Video
Impact of Genetics on Bone Mineral Density and Osteoporosis RiskBone health and genetics -
Vitamin D and calcium play a central role by triggering bone resorption and formation, respectively. Vitamin D also aids in the absorption of calcium. If any part of the remodeling process is imbalanced, bones can start to thin, become brittle, and break.
One cause for the disruption of the process is aging-related changes in hormone levels. This includes natural declines in the sex hormone estrogen after menopause in people who menstruate, which leads to more bone resorption than formation. On the flip side, natural increases in parathyroid hormone PTH in both people of any sex cause calcium to leave the bones and go into the blood, leading to bone mineral loss.
It is for these and other reasons that osteoporosis tends to affect people over 50, most especially postmenopausal females. Genetics is known to further predispose a person to osteoporosis, while various lifestyle factors including nutritional deficiencies, physical inactivity, cigarette smoking, and alcohol use disorder can amplify the risk.
While older age and a low BMD are strong predictors of osteoporosis-related fractures, a family history of osteoporosis also greatly influences the risk. Studies have shown that having a sibling with a low BMD increases your risk of a low BMD by sixfold compared to the general population.
Yet, despite the strong statistical evidence for the heritability of osteoporosis, there remain large gaps in scientists' understanding of how genetics factors into the development and risk of osteoporosis. To better understand how genetics influences bone mineral loss, researchers in the early s turned to the human genome —the complete map of genetic DNA instructions in humans—to search for gene variations common in people with osteoporosis.
Much of the early research was focused on twins in whom certain genes were abnormally positioned on the chromosomes of both people. Based on these and other studies, scientists have identified genetic variants linked to osteoporosis and variants linked to osteoporosis in specific parts of the body such as the hip or lower spine.
Other variants still are able to predict a person's risk of a fracture from osteoporosis based on the pattern of bone mineral loss. To date, no fewer than 71 genetic variants associated with osteoporosis have been found. Some of the associations are stronger than others, and it is possible that multiple genetic variants may contribute to the overall risk of the disease.
Despite progress in genetic research, scientists have yet to establish a clear association between osteoporosis and the different genetic variants.
While certain variants may predispose you to osteoporosis, having one or even several variants doesn't mean you will get osteoporosis. Other factors, such as a person's age, weight, and sex, can ultimately determine how consequential or inconsequential a variant is.
Scientists today believe that the different genetic variants contribute to osteoporosis by interfering with specific, unique processes involved in bone remodeling. These include:. By better understanding how genes contribute to the onset or progression of osteoporosis, scientists may one day be able to develop drugs that can block these and other processes that contribute to bone mineral loss.
Even beyond a person's age and genetic predisposition for osteoporosis, there are numerous other factors that can contribute to the overall risk of bone mineral loss. Some factors are modifiable changeable , while others are unmodifiable unchangeable.
The most common risk factors for osteoporosis include:. Females 50 and over have a fourfold greater risk of osteoporosis compared to their male counterparts. This is not only due to declines in estrogen during menopause but also because females tend to have smaller frames and have less bone mass to draw upon as they age.
Malnutrition plays a major role in osteoporosis by depriving the body of the nutrients needed to maintain bone health, most notably calcium and vitamin D. But calcium and vitamin D are only part of the picture. The inadequate intake of protein contributes to osteoporosis-related fractures by reducing BMD and the muscle strength needed to support weakened bones.
Researchers have found that cigarette smoke causes bone mineral loss both directly and indirectly:. Chronic, heavy alcohol use decreases bone density and destabilizes the matrix of osteoclasts that give bones their strength and resistance to impact. It does so by interfering with the production of vitamin D, which calcium needs to be absorbed.
Without ample calcium, bone formation is weakened. Chronic, heavy alcohol use can also reduce estrogen levels in females and testosterone levels in males, both of which contribute to bone mineral loss and impaired bone remodeling. Any chronic medical condition that interferes with the process of bone remodeling can contribute to osteoporosis.
It can do so by causing nutritional deficiencies, impeding the absorption of calcium or vitamin D, altering hormone levels, or provoking a chronic inflammatory response that disrupts the normal production of osteoclasts.
These include medical conditions such as:. Many drugs can affect bone metabolism. Some affect hormone levels, inhibit calcium absorption, disrupt the balance of vitamin D and calcium, or interfere with bone resorption.
Substances affecting the bones include:. Data from the ongoing National Health and Nutrition Examination Survey NHANES has shown that osteoporosis generally is diagnosed more often in White people It is unclear what role genetics may play in this, but researchers have identified several factors that may contribute to the disparity:.
Osteoporosis is diagnosed when a person's BMD falls below 2. A standard deviation is a statistical value used to describe the amount of variation from the norm.
Osteoporosis is currently defined as follows:. BMD is typically measured with an imaging tool called a dual-energy X-ray absorptiometry DEXA scan. A DEXA scan works by using two different X-ray beams to differentiate bone from other tissues.
It is a simple, noninvasive imaging tool that delivers a low radiation dose and does not involve drugs or contrast agents. The U. Preventive Services Task Force USPTF recommends osteoporosis screening for all females 65 years of age and older as well as postmenopausal females under 65 with risk factors for osteoporosis.
The USPTF has not offered any recommendations regarding osteoporosis screening in males due to the lack of evidence supporting its benefits. While some risk factors for osteoporosis are unmodifiable, there are others you can change, despite your genetic predisposition for the disease.
According to the National Institute on Aging, the five key measures you can take to prevent osteoporosis or the risk of fractures from osteoporosis are:. Genetics is thought to predispose certain people to osteoporosis, particularly those with a family history of the disease.
Even so, there remain questions as to how genes influence the risk of osteoporosis and which genes or combination of genes are most likely to cause bone mineral loss. In the end, genes only play a part in a person's overall risk of osteoporosis in tandem with other risk factors such as older age, smoking, alcohol abuse, malnutrition, and co-occurring medical conditions.
There are numerous things you can do to prevent or slow the progression of osteoporosis. J Am Geriatr Soc 42 : — Hayes WC , Myers ER , Morris JN , Gerhart TN , Yett HS , Lipsitz LA Impact near the hip dominates fracture risk in elderly nursing home residents who fall.
Calcif Tissue Int 52 : — Nordin BEC , Peacock M , Aaron J , Crilly RG , Heyburn PJ , Horsman A , Marshall DH Osteoporosis and osteomalacia. Clin Endocrinol Metab 9 : — Slemenda CW , Turner CH , Peacock M , Christian JC , Sorbel J , Hui SL , Johnston CC The genetics of proximal femur geometry, distribution of bone mass and bone mineral density.
Osteoporos Int 6 : — Frost HM The role of changes in mechanical usage set points in the pathogenesis of osteoporosis.
J Bone Miner Res 7 : — Melton LJ , III Epidemiology of spinal osteoporosis. Spine 22 Suppl :2S—11S. Kannus P , Parkkari J , Sievänen H, Heinonen A, Vuori I, Järvinen M Epidemiology of hip fractures. Bone 18 Suppl S—63S. Silverman SL , Madison RE Decreased incidence of hip fracture in Hispanics, Asians, and Blacks: California hospital discharge data.
Am J Public Health 78 : — Kellie SE , Brody JA Sex-specific and race-specific hip fracture rates. Am J Public Health 80 : — Tinetti ME , Speechley M , Ginter SF Risk factors for falls among elderly persons living in the community. Snedecor GW , Cochran WG Statistical methods.
Ames, IA : The Iowa State University Press. Pocock NA , Eisman JA , Hopper JL , Yeates MG , Sambrook PN , Ebert S Genetic determinants of bone mass in adults: a twin study.
J Clin Invest 80 : — Slemenda CW , Christian JC , Williams CJ , Norton JA , Johnston Jr CC Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates.
J Bone Miner Res 6 : — Hustmyer FG , Peacock M , Hui S , Johnston CC , Christian J Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus. J Clin Invest 94 : — Koller DL , Peacock M , Conneally PM , Liu G , Hui SL , McClintock R , Christian JC , Johnston CC , Econs MJ , Foroud T Heritability of bone-related phenotypes in Caucasian and African-American sister pairs.
Am J Hum Genet A Abstract. Smith DM , Nance WE , Kang KW , Christian JC , Johnston Jr CC Genetic factors in determining bone mass.
J Clin Invest 52 : — Moller M , Horsman A , Harvald B , Hauge M , Henningsen K , Nordin BEC Metacarpal morphometry in monozygotic and dizygotic elderly twins. Calcif Tiss Res 25 : — Dequeker J , Nijs N , Verstraeten A , Geusens P , Gevers G Genetic determinants of bone mineral content at the spine and radius: a twin study.
Bone 8 : — Sowers MR , Burns TL , Wallace RB Familial resemblance of bone mass in adult women. Genet Epidemiol 3 Suppl : 85 — Am J Clin Nutr 44 : 99 — Tylavsky FA , Bortz AD , Hancock RL , Anderson JJ Familial resemblance of radial bone mass between premenopausal mothers and their college-age daughters.
Calcif Tissue Int 45 : — Lutz J , Tesar R Mother-daughter pairs: spinal and femoral bone densities and dietary intakes.
Am J Clin Nutr 52 : — Sowers MR , Boehnke M , Jannausch ML , Crutchfield M , Corton G , Burns TL Familiality and partitioning the variability of femoral bone mineral density in women of child-bearing age. Calcif Tissue Int 50 : — Gueguen R , Jouanny P , Guillemin F , Kuntz C , Pourel J , Siest G Segregation analysis and variance components analysis of bone mineral density in healthy families.
J Bone Miner Res 10 : — Koller DL , Econs MJ , Morin PA , Christian JC , Hui SL , Parry P , Curran ME , Rodriguez LA , Conneally PM , Joslyn G , Peacock M , Johnston CC , Foroud T Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.
J Clin Endocrinol Metab 85 : — Seeman E , Hopper JL , Back LA , Cooper ME , Parkinson E , McKay J , Jermus G Reduced bone mass in daughters of women with osteoporosis.
Seeman E , Tsalamandris C , Formica C , Hopper JL , McKay J Reduced femoral neck bone density in the daughters of women with hip fractures: the role of low peak bone density in the pathogenesis of osteoporosis.
Danielson ME , Cauley JA , Baker CE , Newman AB , Dorman JS , Towers JD , Kuller LH Familial resemblance of bone mineral density BMD and calcaneal ultrasound attenuation: the BMD in mothers and daughters study.
J Bone Miner Res 14 : — Lonzer MD , Imrie R , Rogers D , Worley D , Licata A , Secic M Effects of heredity, age, weight, puberty, activity, and calcium intake on bone mineral density in children.
Clin Pediatr Phila 35 : — Ferrari S , Rizzoli R , Slosman D , Bonjour JP Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab 83 : — Orwoll ES , Belknap JK , Klein RF Gender specificity in the genetic determinants of peak bone mass.
Holzinger KJ The relative effect of nature and nurture influences on twin differences. J Educ Psychol 20 : — Clark PJ The heritability of certain anthropometric characters as ascertained from measurements of twins.
Feinleib M , Garrison RJ , Fabsitz R , Christian JC , Hrubec Z , Borhani NO , Kannel WB , Rosenman R , Schwartz JT , Wagner JO The NHLBI Twin Study of Cardiovascular Disease Risk Factors: methodology and summary of results.
Arden NK , Baker J , Hogg C , Baan K , Spetor TD The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins.
Koller DL , Liu GD , Econs MJ , Hui SL , Morin PA , Joslyn G , Rodriguez LA , Conneally PM , Christian JC , Johnston Jr CC , Foroud T , Peacock M Genome screen for quantitative trait loci underlying normal variation in femoral structure.
Koller DL , Liu G , Econs MJ , Hui SL , Conneally PM , Johnston Jr CC , Foroud T , Peacock M Genome screen for QTLs underlying normal variation in vertebral structure. J Bone Miner Res 16 Suppl :S Christian JC , Yu P-L , Slemenda CW , Johnston Jr CC Heritability of bone mass: a longitudinal study in aging male twins.
Am J Hum Genet 44 : — Kelly PJ , Nguyen T , Hopper J , Pocock N , Sambrook P , Eisman J Changes in axial bone density with age: a twin study. J Bone Miner Res 8 : 11 — Delmas PD Biochemical markers of bone turnover. J Bone Miner Res 8 Suppl 2 : S — S Weaver CM , Peacock M , Martin BR , McCabe GP , Zhao J , Smith DL , Wastney ME Quantification of biochemical markers of bone turnover by kinetic measures of bone formation and resorption in young healthy females.
Kleerekoper M , Nelson DA , Peterson EL , Flynn MJ , Pawluszka AS , Jacobsen G , Wilson P Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older 55—75 postmenopausal white and black women. Greenspan SL , Parker RA , Ferguson L , Rosen HN , Maitland-Ramsey L , Karpf DB Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.
J Bone Miner Res 13 : — Bauer DC , Sklarin P , Stone KL , Black DM , Nevitt MC , Ensrud KE , Arnaud CD , Genant HK , Garnero P , Delmas PD , Lawaetz H , Cummings SR Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. Ross PD , Knowlton W Rapid bone loss is associated with increased levels of biochemical markers.
Kelly PJ , Hopper JL , Macaskill GT , Pocock NA , Sambrook PN , Eisman JA Genetic factors in bone turnover. J Clin Endocrinol Metab 72 : — Livshits G , Yakovenko C , Kobyliansky E Quantitative genetic analysis of circulating levels of biochemical markers of bone formation.
Am J Med Genet 94 : — Cummings SR , Nevitt MC , Browner WS , Stone K , Fox KM , Ensrud KE , Cauley J , Black D , Vogt TM Risk factors for hip fracture in white women. Kannus P , Palvanen M , Kaprio J , Parkkari J , Koskenvuo M Genetic factors and osteoporotic fracture in elderly people: prospective 25 year follow up of a nationwide cohort of elderly Finnish twins.
MacGregor A , Sneider H , Spector TD Genetic factors and osteoporotic fractures in elderly people: twin data support genetic contribution to risk of fracture. Br Med J : Carmelli D , Kelly-Hayes M , Wolf PA , Swan GE , Jack LM , Reed T , Guralnik JM The contribution of genetic influences to measures of lower-extremity function in older male twins.
J Gerontol [A] 55A : B49 — B Wark JD , Hill K , Cassano AM , El Haber N , MacInnis R Genetic effects on falls risk may help explain why fractures run in families: a twin study. Bone 28 Suppl :S72 Abstract. Sheldon JH On the natural history of falls in old age.
Br Med J — Tinetti ME , Williams CS Falls, injuries due to falls, and the risk of admission to a nursing home.
Campbell A , Reinken J , Allan B , Martinez G Falls in old age: a study of frequency and related clinical factors.
Age Ageing 10 : — Lauritzen JB , Petersen MM , Lund B Effect of external hip protectors on hip fractures. Lancet : 11 — Rubenstein L Hip protectors—a breakthrough in fracture prevention.
Rubenstein LZ , Robbins AS , Schulman BL , Rosado J , Osterweil D , Josephson KR Falls and instability in the elderly.
J Am Geriatr Soc 36 : — Kelsey JL , Hoffman S Risk factors for hip fracture. Nevitt MC , Cummings SR , Kidd S , Black D Risk factors for recurrent nonsyncopal falls: a prospective study. JAMA : — Ho NC , Libin J , Driscoll CC , Gutter EM , Francomano CA A skeletal gene database.
Risch N , Merikangas K The future of genetic studies of complex human diseases. Spielman RS , Ewens WJ The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 59 : — Pritchard JK , Rosenberg NA Use of unlinked genetic markers to detect population stratification in association studies.
Am J Hum Genet 65 : — Pritchard JK , Stephens M , Rosenberg NA , Donnelly P Association mapping in structured populations. Am J Hum Genet 67 : — Nat Genet 29 : — Daly MJ , Rioux JD , Schaffner SF , Hudson TJ , Lander ES High-resolution haplotype structure in the human genome. Johnson GC , Esposito L , Barratt BJ , Smith AN , Heward J , Di Genova G , Ueda H , Cordell HJ , Eaves IA , Dudbridge F , Twells RC , Payne F , Hughes W , Nutland S , Stevens H , Carr P , Tuomilehto-Wolf E , Tuomilehto J , Gough SC , Clayton DG , Todd JA Haplotype tagging for the identification of common disease genes.
Cooper GS , Umbach DM Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. Barger-Lux MJ , Heaney RP , Hayes J , DeLuca HF , Johnson ML , Gong G Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density.
Calcif Tissue Int 57 : — Lorentzon M , Lorentzon R , Nordström P Vitamin D receptor gene polymorphism is associated with birth height, growth to adolescence, and adult stature in healthy Caucasian men: a cross-sectional and longitudinal study.
Keen RW , Egger P , Fall C , Major PJ , Lanchbury JS , Spector TD , Cooper C Polymorphisms of the vitamin D receptor, infant growth, and adult bone mass. Calcif Tissue Int 60 : — Kitagawa I , Kitagawa Y , Kawase Y , Nagaya T , Tokudome S Advanced onset of menarche and higher bone mineral density depending on vitamin D receptor gene polymorphism.
Eur J Endocrinol : — Geusens P , Vandevyver C , Vanhoof J , Cassiman JJ , Boonen S , Raus J Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. Gennari L , Becherini L , Masi L , Gonnelli S , Cepollaro C , Martini S , Mansani R , Brandi ML Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women.
Calcif Tissue Int 61 : — Kiel DP , Myers RH , Cupples LA , Kong XF , Zhu XH , Ordovas J , Schaefer EJ , Felson DT , Rush D , Wilson PW , Eisman JA , Holick MF The Bsm I vitamin D receptor restriction fragment length polymorphism bb influences the effect of calcium intake on bone mineral density.
Ongphiphadhanakul B , Rajatanavin R , Chanprasertyothin S , Chailurkit L , Piaseu N , Teerarungsikul K , Sirisriro R , Komindr S , Puavilai G Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women.
J Endocrinol Invest 20 : — Schwartz BS , Lee BK , Lee GS , Stewart WF , Simon D , Kelsey K , Todd AC Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and δ-aminolevulinic acid dehydratase genes.
Environ Health Perspect : — Lee BK , Lee GS , Stewart WF , Ahn KD , Simon D , Kelsey KT , Todd AC , Schwartz BS Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and δ-aminolevulinic acid dehydratase genes.
World J Surg 22 : — Chang TJ , Lei HH , Yeh JI , Chiu KC , Lee KC , Chen MC , Tai TY , Chuang LM Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population.
Clin Endocrinol Oxf 52 : — Fernández E , Fibla J , Betriu A , Piulats JM , Almirall J , Montoliu J Association between vitamin D receptor gene polymorphism and relative hypoparathyroidism in patients with chronic renal failure.
J Am Soc Nephrol 8 : — Fischer PR , Thacher TD , Pettifor JM , Jorde LB , Eccleshall TR , Feldman D Vitamin D receptor polymorphisms and nutritional rickets in Nigerian children.
Ortlepp JR , Hoffmann R , Ohme F , Lauscher J , Bleckmann F , Hanrath P The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart 85 : — Fukazawa T , Yabe I , Kikuchi S , Sasaki H , Hamada T , Miyasaka K , Tashiro K Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese.
J Neurol Sci : 47 — Videman T , Leppävuori J , Kaprio J , Battié MC , Gibbons LE , Peltonen L , Koskenvuo M Volvo Award winner in basic science studies—intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 23 : — Uitterlinden AG , Burger H , Huang QJ , Odding E , Van Duijn CM , Hofman A , Birkenhäger JC , Van Leeuwen JP , Pols HA Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.
J Clin Invest : — Halmos B , Szalay F , Cserniczky T , Nemesanszky E , Lakatos P , Barlage S , Schmitz G , Romics L , Csaszar A Association of primary biliary cirrhosis with vitamin D receptor BsmI genotype polymorphism in a Hungarian population.
Dig Dis Sci 45 : — Bretherton-Watt D , Given-Wilson R , Mansi JL , Thomas V , Carter N , Colston KW Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Br J Cancer 85 : — Garcia-Lozano JR , Gonzalez-Escribano MF , Valenzuela A , Garcia A , Núñez-Roldán A Association of vitamin D receptor genotypes with early onset rheumatoid arthritis.
Eur J Immunogenet 28 : 89 — Habuchi T , Suzuki T , Sasaki R , Wang LZ , Sato K , Satoh S , Akao T , Tsuchiya N , Shimoda N , Wada Y , Koizumi A , Chihara J , Osamu OA , Kato T Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population.
Cancer Res 60 : — Bellamy R Identifying genetic susceptibility factors for tuberculosis in Africans: a combined approach using a candidate gene study and a genome-wide screen. Clin Sci 98 : — Eichner JE , Friedrich CA , Cauley JA , Kamboh MI , Gutai JP , Kuller LH , Ferrell RE α 2 -HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women.
Calcif Tissue Int 47 : — Dickson IR , Gwilliam R , Arora M , Murphy S , Khaw K-T , Phillips C , Lincoln P Lumbar vertebral and femoral neck bone mineral density are higher in postmenopausal women with the α 2 HS-glycoprotein 2 phenotype.
Bone Miner 24 : — Dickson IR , Poole AR , Veis A Localization of plasma α HS-glycoprotein in mineralizing human bone. Malone JD , Richards M α2 HS-glycoprotein is chemotactic for mononuclear phagocytes.
J Cell Physiol : — Haussler MR , Haussler CA , Jurutka PW , Thompson PD , Hsieh JC , Remus LS , Selznick SH , Whitfield GK The vitamin D hormone and its nuclear receptor: molecular actions and disease states.
J Endocrinol Suppl :S57—S Morrison NA , Qi JC , Tokita A , Kelly PJ , Crofts L , Nguyen TV , Sambrook PN , Eisman JA Prediction of bone density from vitamin D receptor alleles. Peacock M , Hustmyer FG , Hui S , Johnston CC , Christian J Vitamin D receptor genotype and bone mineral density—evidence conflicts on link.
Morrison NA , Qi JC , Tokita A , Kelly PJ , Crofts L , Nguyen TV , Sambrook PN , Eisman JA Prediction of bone density from vitamin D receptor alleles: corrections. Nature : Zee RYL , Myers RH , Hannan MT , Wilson PWF , Ordovas JM , Schaefer EJ , Lindpaintner K , Kiel DP Absence of linkage for bone mineral density to chromosome 12q12—14 in the region of the vitamin D receptor gene.
Calcif Tissue Int 67 : — Parker MG , Arbuckle N , Dauvois S , Danielian P , White R Structure and function of the estrogen receptor.
Ann NY Acad Sci : — Kuiper GGJM , Enmark E , Pelto-Huikko M , Nilsson S , Gustafsson J-A Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93 : — MacGillivray MH , Morishima A , Conte F , Grumbach M , Smith EP Pediatric endocrinology update: an overview—the essential roles of estrogens in pubertal growth, epiphyseal fusion and bone turnover: lessons from mutations in the genes for aromatase and the estrogen receptor.
Lindsay R The role of estrogen in the prevention of osteoporosis. Endocrinol Metabol Clin North Am 27 : — Sano M , Inoue S , Hosoi T , Ouchi Y , Emi M , Shiraki M , Orimo H Association of estrogen receptor dinucleotide repeat polymorphism with osteroporosis.
Biochem Biophys Res Commun : — Kobayashi S , Inoue S , Hosoi T , Ouchi Y , Shiraki M , Orimo H Association of bone mineral density with polymorphism of the estrogen receptor gene. Han KO , Moon IG , Kang YS , Chung HY , Min HK , Han IK Nonassociation of estrogen receptor genotypes with bone mineral density and estrogen responsiveness to hormone replacement therapy in Korean postmenopausal women.
J Clin Endocrinol Metab 82 : — Bagger YZ , Jorgensen HL , Heegaard AM , Bayer L , Hansen L , Hassager C No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women. Bone 26 : — Ogawa S , Hosoi T , Shiraki M , Orimo H , Emi M , Muramatsu M , Ouchi Y , Inoue S Association of estrogen receptor β gene polymorphism with bone mineral density.
Grant SF , Reid DM , Blake G , Herd R , Fogelman I , Ralston SH Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I α 1 gene. Nat Genet 14 : — Garnero P , Borel O , Grant SF , Ralston SH , Delmas PD Collagen Iα1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premenopausal women: the OFELY study.
Hustmyer FG , Liu G , Johnston CC , Christian J , Peacock M Polymorphism at an Sp1 binding site of COL1A1 and bone mineral density in premenopausal female twins and elderly fracture patients.
Osteoporos Int 9 : — Willing MC , Torner JC , Burns TL , Segar ET , Werner JR Determinants of bone mineral density in postmenopausal white Iowans. J Gerontol [A] 52A : M — M Hum Immunol 59 : — Shiraki M , Shiraki W , Aoki C , Hosoi T , Inoue S , Kaneki M , Ouchi Y Association of bone mineral density with apolipoprotein E phenotype.
Heikkinen AM , Kröger H , Niskanen L , Komulainen MH , Ryynänen M , Parviainen MT , Tuppurainen MT , Honkanen R , Saarikoski S Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?
Maturitas 34 : 33 — Salamone LM , Cauley JA , Zmuda J , Pasagian-Macaulay A , Epstein RS , Ferrell RE , Black DM , Kuller LH Apolipoprotein E gene polymorphism and bone loss: estrogen status modifies the influence of apolipoprotein E on bone loss.
Duncan EL , Brown MA , Sinsheimer J , Bell J , Carr AJ , Wordsworth BP , Wass JAH Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. Ota N , Hunt SC , Nakajima T , Suzuki T , Hosoi T , Orimo H , Shirai Y , Emi M Linkage of interleukin 6 locus to human osteopenia by sibling pair analysis.
Hum Genet : — Ota N , Hunt SC , Nakajima T , Suzuki T , Hosoi T , Shirai Y , Emi M Linkage of human tumor necrosis factor-α to human osteoporosis by sib pair analysis. Genes Immunity 1 : — Spielman RS , McGinnis RE , Ewens WJ Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus IDDM.
Am J Hum Genet 52 : — McGinnis RE , Ewens WJ , Spielman RS The TDT reveals linkage and linkage disequilibrium in a rare disease.
Genet Epidemiol 12 : — Am J Hum Genet 62 : — Boehnke M , Langefeld CD Genetic association mapping based on discordant sib pairs: the discordant-allele test. Curtis D Use of siblings as controls in case-control association studies.
Ann Hum Genet 61 : — Martin ER , Monks SA , Warren LL , Kaplan NL A test for linkage and association in general pedigrees: the pedigree disequilibrium test. Allison DB Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet 60 : — Allison DB , Heo M , Kaplan N , Martin ER Sibling-based tests of linkage and association for quantitative traits.
Am J Hum Genet 64 : — Ann Hum Genet 64 : — Genet Epidemiol 20 : 57 — Schaffer AA , Gupta SK , Shriram K , Cottingham Jr RW Avoiding recomputation in linkage analysis. Hum Hered 44 : — Nat Genet 11 : — Sham PC , Lin MW , Zhao JH , Curtis D Power comparison of parametric and nonparametric linkage test in small pedigrees.
Am J Hum Genet 66 : — Kruglyak L , Lander ES Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57 : — Almasy L , Blangero J Multipoint quantitative-trait linkage analysis in general pedigrees. Johnson ML , Gong GD , Kimberling W , Recker SM , Kimmel DB , Recker RR Linkage of a gene causing high bone mass to human chromosome 11 11q12— Recker RR , Johnson ML , Davies KM , Recker SM , Heaney RP Autosomal dominant high bone mass: the phenotype.
J Bone Miner Res 16 Suppl :S Abstract. Whyte MP Sclerosing bone dysplasias. In: Favus MJ , ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. Philadelphia : Lippincott-Raven ; — Little RD , Carulli JP , Del Mastro RG , Dupuis J , Osborne M , Folz C , Manning SP , Swain PM , Zhao S-C , Eustace B , Lappe MM , Spitzer L , Zweier S , Braunschweiger K , Benchekroun Y , Hu X , Adair R , Chee L , FitzGerald MG , Tulig C , Caruso A , Tzellas N , Bawa A , Franklin B , McGuire S , Nogues X , Gong G , Allen KM , Anisowicz A , Morales AJ , Lomedico PT , Recker SM , Eerdewegh PV , Recker RR , Johnson ML A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone mass trait.
Am J Hum Genet 70 : 11 — Tamai K , Semenov M , Kato Y , Spokony R , Liu CM , Katsuyama Y , Hess F , Saint-Jeannet JP , He X LDL-receptor-related proteins in Wnt signal transduction. Spotila LD , Caminis J , Devoto M , Shimoya K , Sereda L , Ott J , Whyte MP , Tenenhouse A , Prockop DJ Osteopenia in 37 members of seven families: analysis based on a model of dominant inheritance.
Mol Med 2 : — Devoto M , Shimoya K , Caminis J , Ott J , Tenenhouse A , Whyte MP , Sereda L , Hall S , Considine E , Williams CJ , Tromp G , Kuivaniemi H , Ala-Kokko L , Prockop DJ , Spotila LD First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q.
Eur J Hum Genet 6 : — Cardon LR , Garner C , Bennett ST , MacKay IJ , Edwards RM , Cornish J , Hegde M , Murray MAF , Reid IR , Cundy T Evidence for a major gene for bone mineral density in idiopathic osteoporotic families.
Koller DL , Rodriguez LA , Christian JC , Slemenda CW , Econs MJ , Hui SL , Morin P , Conneally PM , Joslyn G , Curran ME , Peacock M , Johnston CC , Foroud T Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12— Frattini A , Orchard PJ , Sobacchi C , Giliani S , Abinun M , Mattsson JP , Keeling DJ , Andersson AK , Wallbrandt P , Zecca L , Notarangelo LD , Vezzoni P , Villa A Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis.
Nat Genet 25 : — Deng HW , Xu FH , Conway T , Deng XT , Li JL , Davies KM , Deng HY , Johnson M , Recker RR Is population bone mineral density variation linked to the marker D11S on chromosome 11q12—13?
J Clin Endocrinol Metab 86 : — Navbar Search Filter Endocrine Reviews This issue Endocrine Society Journals Clinical Medicine Endocrinology and Diabetes Medicine and Health Books Journals Oxford Academic Mobile Enter search term Search. Endocrine Society Journals.
Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Locating the Susceptibility Genes.
Identification of the Susceptibility Genes. Animal Studies. Journal Article. Genetics of Osteoporosis. Munro Peacock , Munro Peacock. Oxford Academic. Charles H.
Michael J. Tatiana Foroud. PDF Split View Views. Cite Cite Munro Peacock, Charles H. Select Format Select format. ris Mendeley, Papers, Zotero.
enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Endocrine Reviews This issue Endocrine Society Journals Clinical Medicine Endocrinology and Diabetes Medicine and Health Books Journals Oxford Academic Enter search term Search.
Abstract Osteoporosis is a common multifactorial disorder of reduced bone mass. Open in new tab Download slide. TABLE 1 Environmental risk factors for osteoporosis. Risk Factor. Open in new tab.
TABLE 2 Heritability H 2 estimates. Sibling pairs n. Lumbar spine BMD 0. TABLE 3 Association studies with candidate genes and BMD. Candidate gene. AHSG α 2 HS-glycoprotein 3q27 , VDR VDR 12q12—q14 76 , 1 , , 1 ESR1 ER 1 α 6q TABLE 4 Results of sibling pair linkage analysis of markers close or within candidate genes with BMD LOD score.
Hip BMD. Spine BMD. PTHR1 Parathyroid hormone receptor 1 3p22—p TABLE 5 Linkage of BMD using a genome screen in pairs of sisters TABLE 6 Linkage of bone structure using a genome screen in pairs of sisters TABLE 7 QTL for BMD in mice from four different laboratories , , , Map position.
Method and skeletal site. Human syntenic region. Wesley Beamer. TABLE 8 Skeletal phenotypes in knockout and transgenic mice. Human chromosome. lipoprotein acceptor-related protein;. transmission disequilibrium test;. Google Scholar OpenURL Placeholder Text.
Google Scholar PubMed. OpenURL Placeholder Text. Google Scholar Crossref. Gong Y , Slee RB , Fukai N , Rawadi G , Roman-Roman S , Reginato AM , Wang H , Cundy T , Glorieux FH , Lev D , Zacharin M , Oexle K , Marcelino J , Suwairi W , Heeger S , Sabatakos G , Apte S , Adkins WN , Allgrove J , Arslan-Kirchner M , Batch JA , Beighton P , Black GC , Boles RG , Boon LM , Borrone C , Brunner HG , Carle GF , Dallapiccola B , De Paepe A , Floege B , Halfhide ML , Hall B , Hennekam RC , Hirose T , Jans A , Jüppner H , Kim CA , Keppler-Noreuil K , Kohlschuetter A , LaCombe D , Lambert M , Lemyre E , Letteboer T , Peltonen L , Ramesar RS , Romanengo M , Somer H , Steichen-Gersdorf E , Steinmann B , Sullivan B , Superti-Furga A , Swoboda W , van den Boogaard MJ , Van Hul W , Vikkula M , Votruba M , Zabel B , Garcia T , Baron R , Olsen BR , Warman ML LDL receptor-related protein 5 LRP5 affects bone accrual and eye development.
Cell : — Little RD , Carulli JP , Del Mastro RG , Dupuis J , Osborne M , Folz C , Manning SP , Swain PM , Zhao SC , Eustace B , Lappe MM , Spitzer L , Zweier S , Braunschweiger K , Benchekroun Y , Hu X , Adair R , Chee L , FitzGerald MG , Tulig C , Caruso A , Tzellas N , Bawa A , Franklin B , McGuire S , Nogues X , Gong G , Allen KM , Anisowicz A , Morales AJ , Lomedico PT , Recker SM , Van Eerdewegh P , Recker RR , Johnson ML A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.
Am J Hum Genet 70 : 11 — Ferrari SL , Deutsch S , Choudhury U , Chevalley T , Bonjour JP , Dermitzakis ET , Rizzoli R , Antonarakis SE Polymorphisms in the low-density lipoprotein receptor-related protein 5 LRP5 gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.
Am J Hum Genet 74 : — Koay MA , Woon PY , Zhang Y , Miles LJ , Duncan EL , Ralston SH , Compston JE , Cooper C , Keen R , Langdahl BL , MacLelland A , O'Riordan J , Pols HA , Reid DM , Uitterlinden AG , Wass JA , Brown MA Influence of LRP5 polymorphisms on normal variation in BMD.
J Bone Miner Res 19 : — Koh JM , Jung MH , Hong JS , Park HJ , Chang JS , Shin HD , Kim SY , Kim GS Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men.
J Korean Med Sci 19 : — Balemans W , Patel N , Ebeling M , Van Hul E , Wuyts W , Lacza C , Dioszegi M , Dikkers FG , Hildering P , Willems PJ , Verheij JB , Lindpaintner K , Vickery B , Foernzler D , Van Hul W Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease.
J Med Genet 39 : 91 — Am J Hum Genet 75 : — Sims AM , Shephard N , Carter K , Doan T , Dowling A , Duncan EL , Eisman J , Jones G , Nicholson G , Prince R , Seeman E , Thomas G , Wass JA , Brown MA Genetic analyses in a sample of individuals with high or low bone density demonstrates association with multiple Wnt pathway genes.
Ng SB , Turner EH , Robertson PD , Flygare SD , Bigham AW , Lee C , Shaffer T , Wong M , Bhattacharjee A , Eichler EE , Bamshad M , Nickerson DA , Shendure J Targeted capture and massively parallel sequencing of 12 human exomes. Nature : — Mamm Genome 16 : — Koller DL , Liu L , Alam I , Sun Q , Econs MJ , Foroud T , Turner CH Epistatic effects contribute to variation in bone density in Fischer x Lewis F2 rats.
J Bone Miner Res 23 : 41 — Carlborg O , Hocking PM , Burt DW , Haley CS Simultaneous mapping of epistatic QTL in chickens reveals clusters of QTL pairs with similar genetic effects on growth. Genet Res 83 : — Varona L , Ovilo C , Clop A , Noguera JL , Pérez-Enciso M , Coll A , Folch JM , Barragán C , Toro MA , Babot D , Sánchez A QTL mapping for growth and carcass traits in an Iberian by Landrace pig intercross: additive, dominant and epistatic effects.
Genet Res 80 : — Nat Genet 14 : — Lehner B Modelling genotype-phenotype relationships and human disease with genetic interaction networks. J Exp Biol : — Padyukov L , Silva C , Stolt P , Alfredsson L , Klareskog L A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis.
Arthritis Rheum 50 : — Sykes B , Ogilvie D , Wordsworth P , Wallis G , Mathew C , Beighton P , Nicholls A , Pope FM , Thompson E , Tsipouras P , Schwartz R , Jensson O , Arnason A , Børresen A-L , Heiberg A , Frey D , Steinmann B Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.
Am J Hum Genet 46 : — Gong Y , Vikkula M , Boon L , Liu J , Beighton P , Ramesar R , Peltonen L , Somer H , Hirose T , Dallapiccola B , De Paepe A , Swoboda W , Zabel B , Superti-Furga A , Steinmann B , Brunner HG , Jans A , Boles RG , Adkins W , van den Boogaard MJ , Olsen BR , Warman ML Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12— Am J Hum Genet 59 : — Johnson ML , Gong G , Kimberling W , Reckér SM , Kimmel DB , Recker RB Linkage of a gene causing high bone mass to human chromosome 11 11q12— Am J Hum Genet 60 : — Bénichou O , Cleiren E , Gram J , Bollerslev J , de Vernejoul MC , Van Hul W Mapping of autosomal dominant osteopetrosis type II Albers-Schonberg disease to chromosome 16p Am J Hum Genet 69 : — Chodirker BN , Evans JA , Lewis M , Coghlan G , Belcher E , Philipps S , Seargeant LE , Sus C , Greenberg CR Infantile hypophosphatasia—linkage with the RH locus.
Genomics 1 : — Balemans W , Van Den Ende J , Freire Paes-Alves A , Dikkers FG , Willems PJ , Vanhoenacker F , de Almeida-Melo N , Alves CF , Stratakis CA , Hill SC , Van Hul W Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12—q Am J Hum Genet 64 : — Van Hul W , Balemans W , Van Hul E , Dikkers FG , Obee H , Stokroos RJ , Hildering P , Vanhoenacker F , Van Camp G , Willems PJ Van Buchem disease hyperostosis corticalis generalisata maps to chromosome 17q12—q Am J Hum Genet 62 : — Deng HW , Xu FH , Huang QY , Shen H , Deng H , Conway T , Liu YJ , Liu YZ , Li JL , Zhang HT , Davies KM , Recker RR A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait loci for osteoporosis.
J Clin Endocrinol Metab 87 : — Koller DL , Econs MJ , Morin PA , Christian JC , Hui SL , Parry P , Curran ME , Rodriguez LA , Conneally PM , Joslyn G , Peacock M , Johnston CC , Foroud T Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.
J Clin Endocrinol Metab 85 : — Devoto M , Specchia C , Li HH , Caminis J , Tenenhouse A , Rodriguez H , Spotila LD Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p Hum Mol Genet 10 : — Styrkarsdottir U , Cazier JB , Kong A , Rolfsson O , Larsen H , Bjarnadottir E , Johannsdottir VD , Sigurdardottir MS , Bagger Y , Christiansen C , Reynisdottir I , Grant SF , Jonasson K , Frigge ML , Gulcher JR , Sigurdsson G , Stefansson K Linkage of osteoporosis to chromosome 20p12 and association to BMP2.
PLoS Biol 1 : E Duncan EL , Brown MA , Sinsheimer J , Bell J , Carr AJ , Wordsworth BP , Wass JA Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. J Bone Miner Res 14 : — Ralston SH , Galwey N , MacKay I , Albagha OM , Cardon L , Compston JE , Cooper C , Duncan E , Keen R , Langdahl B , McLellan A , O'Riordan J , Pols HA , Reid DM , Uitterlinden AG , Wass J , Bennett ST Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study.
Hum Mol Genet 14 : — Lander E , Kruglyak L Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11 : — Tranah GJ , Taylor BC , Lui LY , Zmuda JM , Cauley JA , Ensrud KE , Hillier TA , Hochberg MC , Li J , Rhees BK , Erlich HA , Sternlicht MD , Peltz G , Cummings SR Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures.
Calcif Tissue Int 83 : — Medici M , van Meurs JB , Rivadeneira F , Zhao H , Arp PP , Hofman A , Pols HA , Uitterlinden AG BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study. J Bone Miner Res 21 : — Bonekey-Osteovision 2 : 14 — Richards JB , Kavvoura FK , Rivadeneira F , Styrkársdóttir U , Estrada K , Halldórsson BV , Hsu YH , Zillikens MC , Wilson SG , Mullin BH , Amin N , Aulchenko YS , Cupples LA , Deloukas P , Demissie S , Hofman A , Kong A , Karasik D , van Meurs JB , Oostra BA , Pols HA , Sigurdsson G , Thorsteinsdottir U , Soranzo N , Williams FM , Zhou Y , Ralston SH , Thorleifsson G , van Duijn CM , Kiel DP , Stefansson K , Uitterlinden AG , Ioannidis JP , Spector TD Collaborative meta-analysis: associations of candidate genes with osteoporosis and osteoporotic fracture.
Ann Intern Med : — Wellcome Trust Case-Control Consortium Genomewide association study of 14, cases of seven common diseases and controls. Raychaudhuri S , Plenge RM , Rossin EJ , Ng AC , Purcell SM , Sklar P , Scolnick EM , Xavier RJ , Altshuler D , Daly MJ Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions.
PLoS Genetics 5 : e Kiel DP , Demissie S , Dupuis J , Lunetta KL , Murabito JM , Karasik D Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8 Suppl 1 : S Duncan EL , Brown MA Genetic studies in osteoporosis—the end of the beginning.
Arthritis Res Ther 10 : Cho YS , Go MJ , Kim YJ , Heo JY , Oh JH , Ban HJ , Yoon D , Lee MH , Kim DJ , Park M , Cha SH , Kim JW , Han BG , Min H , Ahn Y , Park MS , Han HR , Jang HY , Cho EY , Lee JE , Cho NH , Shin C , Park T , Park JW , Lee JK , Cardon L , Clarke G , McCarthy MI , Lee JY , Lee JK , Oh B , Kim HL A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits.
Nat Genet 41 : — Kung AW , Xiao SM , Cherny S , Li GH , Gao Y , Tso G , Lau KS , Luk KD , Liu JM , Cui B , Zhang MJ , Zhang ZL , He JW , Yue H , Xia WB , Luo LM , He SL , Kiel DP , Karasik D , Hsu YH , Cupples LA , Demissie S , Styrkarsdottir U , Halldorsson BV , Sigurdsson G , Thorsteinsdottir U , Stefansson K , Richards JB , Zhai G , Soranzo N , Valdes A , Spector TD , Sham PC Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies.
Am J Hum Genet 86 : — Styrkarsdottir U , Halldorsson BV , Gretarsdottir S , Gudbjartsson DF , Walters GB , Ingvarsson T , Jonsdottir T , Saemundsdottir J , Center JR , Nguyen TV , Bagger Y , Gulcher JR , Eisman JA , Christiansen C , Sigurdsson G , Kong A , Thorsteinsdottir U , Stefansson K Multiple genetic loci for bone mineral density and fractures.
Rivadeneira F , Styrkársdottir U , Estrada K , Halldórsson BV , Hsu YH , Richards JB , Zillikens MC , Kavvoura FK , Amin N , Aulchenko YS , Cupples LA , Deloukas P , Demissie S , Grundberg E , Hofman A , Kong A , Karasik D , van Meurs JB , Oostra B , Pastinen T , Pols HA , Sigurdsson G , Soranzo N , Thorleifsson G , Thorsteinsdottir U , Williams FM , Wilson SG , Zhou Y , Ralston SH , van Duijn CM , Spector T , Kiel DP , Stefansson K , Ioannidis JP , Uitterlinden AG Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
Richards JB , Rivadeneira F , Inouye M , Pastinen TM , Soranzo N , Wilson SG , Andrew T , Falchi M , Gwilliam R , Ahmadi KR , Valdes AM , Arp P , Whittaker P , Verlaan DJ , Jhamai M , Kumanduri V , Moorhouse M , van Meurs JB , Hofman A , Pols HA , Hart D , Zhai G , Kato BS , Mullin BH , Zhang F , Deloukas P , Uitterlinden AG , Spector TD Bone mineral density, osteoporosis, and osteoporotic fractures: a genomewide association study.
Lancet : — Styrkarsdottir U , Halldorsson BV , Gretarsdottir S , Gudbjartsson DF , Walters GB , Ingvarsson T , Jonsdottir T , Saemundsdottir J , Snorradóttir S , Center JR , Nguyen TV , Alexandersen P , Gulcher JR , Eisman JA , Christiansen C , Sigurdsson G , Kong A , Thorsteinsdottir U , Stefansson K New sequence variants associated with bone mineral density.
Nat Genet 41 : 15 — Xiong DH , Liu XG , Guo YF , Tan LJ , Wang L , Sha BY , Tang ZH , Pan F , Yang TL , Chen XD , Lei SF , Yerges LM , Zhu XZ , Wheeler VW , Patrick AL , Bunker CH , Guo Y , Yan H , Pei YF , Zhang YP , Levy S , Papasian CJ , Xiao P , Lundberg YW , Recker RR , Liu YZ , Liu YJ , Zmuda JM , Deng HW Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups.
Am J Hum Genet 84 : — Kearns AE , Khosla S , Kostenuik PJ Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 29 : — Kubota T , Michigami T , Ozono K Wnt signaling in bone metabolism.
J Bone Miner Metab 27 : — Bänziger C , Soldini D , Schütt C , Zipperlen P , Hausmann G , Basler K Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells.
Oliver L , Halleux C , Morvan F , Hu S , Lu C , Bauer A , Kneissel M , LRP4 is a novel osteoblast and osteocyte expressed specific facilitator of SOST-mediated inhibition of in vitro bone formation. Proc 31st Annual Meeting of American Society for Bone and Mineral Research , Denver, CO , Abstract A Google Preview.
Allan EH , Häusler KD , Wei T , Gooi JH , Quinn JM , Crimeen-Irwin B , Pompolo S , Sims NA , Gillespie MT , Onyia JE , Martin TJ EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts.
J Dent Res 88 : — Blood : — Wang L , Yang L , Debidda M , Witte D , Zheng Y Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Proc Natl Acad Sci USA : — Nampei A , Hashimoto J , Hayashida K , Tsuboi H , Shi K , Tsuji I , Miyashita H , Yamada T , Matsukawa N , Matsumoto M , Morimoto S , Ogihara T , Ochi T , Yoshikawa H Matrix extracellular phosphoglycoprotein MEPE is highly expressed in osteocytes in human bone.
J Bone Miner Metab 22 : — Rowe PS , Kumagai Y , Gutierrez G , Garrett IR , Blacher R , Rosen D , Cundy J , Navvab S , Chen D , Drezner MK , Quarles LD , Mundy GR MEPE has the properties of an osteoblastic phosphatonin and minhibin.
Bone 34 : — Liu YZ , Pei YF , Liu JF , Yang F , Guo Y , Zhang L , Liu XG , Yan H , Wang L , Zhang YP , Levy S , Recker RR , Deng HW Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males. PLoS One 4 : e Lefebvre V , Li P , de Crombrugghe B A new long form of Sox5 L-Sox5 , Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene.
EMBO J 17 : — Smits P , Li P , Mandel J , Zhang Z , Deng JM , Behringer RR , de Crombrugghe B , Lefebvre V The transcription factors L-Sox5 and Sox6 are essential for cartilage formation.
Dev Cell 1 : — Tagariello A , Heller R , Greven A , Kalscheuer VM , Molter T , Rauch A , Kress W , Winterpacht A Balanced translocation in a patient with craniosynostosis disrupts the SOX6 gene and an evolutionarily conserved non-transcribed region.
J Med Genet 43 : — Arnold MA , Kim Y , Czubryt MP , Phan D , McAnally J , Qi X , Shelton JM , Richardson JA , Bassel-Duby R , Olson EN MEF2C transcription factor controls chondrocyte hypertrophy and bone development.
Dev Cell 12 : — Schroeder TM , Nair AK , Staggs R , Lamblin AF , Westendorf JJ Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors.
BMC Genomics 8 : Tantisira KG , Lake S , Silverman ES , Palmer LJ , Lazarus R , Silverman EK , Liggett SB , Gelfand EW , Rosenwasser LJ , Richter B , Israel E , Wechsler M , Gabriel S , Altshuler D , Lander E , Drazen J , Weiss ST Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.
Hum Mol Genet 13 : — Lee NK , Sowa H , Hinoi E , Ferron M , Ahn JD , Confavreux C , Dacquin R , Mee PJ , McKee MD , Jung DY , Zhang Z , Kim JK , Mauvais-Jarvis F , Ducy P , Karsenty G Endocrine regulation of energy metabolism by the skeleton.
J Bone Miner Res 16 : — Kannus P , Palvanen M , Kaprio J , Parkkari J , Koskenvuo M Genetic factors and osteoporotic fractures in elderly people: prospective 25 year follow up of a nationwide cohort of elderly Finnish twins.
BMJ : — MacGregor A , Snieder H , Spector TD Genetic factors and osteoporotic fractures in elderly people. Twin data support genetic contribution to risk of fracture. BMJ —; author reply — Michaëlsson K , Melhus H , Ferm H , Ahlbom A , Pedersen NL Genetic liability to fractures in the elderly.
Arch Intern Med : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account.
Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Genetic Epidemiology of Bone Phenotypes. Genetic Approaches. GWAS in Osteoporosis. Journal Article. Genetic Determinants of Bone Density and Fracture Risk—State of the Art and Future Directions.
Duncan , Emma L. Duncan, University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland , Australia. Oxford Academic. Matthew A. PDF Split View Views. Cite Cite Emma L.
Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Abstract Context: Osteoporosis is a common, highly heritable condition that causes substantial morbidity and mortality, the etiopathogenesis of which is poorly understood.
TABLE 1. Genetic epidemiology studies of fracture risk. First author Ref. of relative pairs. Kannus 88 Finnish 15, twins No increase in MZ concordance for fracture. MZ, Monozygotic twin. Open in new tab. TABLE 2.
Novel genomewide significant findings in osteoporosis studies to date. Study Ref. Putative gene s. BMD P value. Odds ratio. P value. deCODE-1 64 1p36 ZBTB40 rs 9. LS, Lumbar spine. Open in new tab Download slide. The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins.
Google Scholar Crossref. Search ADS. Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. Genetic determinants of bone mineral content at the spine and radius: a twin study. Genetic and environmental correlations between bone formation and bone mineral density: a twin study.
Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. Segregation analysis and variance components analysis of bone mineral density in healthy families.
Genetic and environmental influences on bone mineral density in pre- and post-menopausal women. Associations between maternal peak bone mass and bone mass in prepubertal male and female children. Gender differences in the genetic factors responsible for variation in bone density and ultrasound.
Family history and risk of osteoporotic fracture. Risk of wrist fracture in women is heritable and is influenced by genes that are largely independent of those influencing BMD. Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases.
Osteoporosis, characterized geenetics deteriorated bone microarchitecture and Bohe bone mineral density, is a chronic skeletal hralth with high heealth prevalence. Natural metabolic support related genetocs aging is the most common form and causes significant morbidity healyh mortality. Rare, monogenic forms of osteoporosis Bonne their onset usually grnetics childhood genetcs young adulthood and have Metformin mechanism of action phenotypic features and clinical course depending on the underlying cause. The Bone health and genetics common form is osteogenesis Bone health and genetics genetcis Bone health and genetics gendtics in COL1A1 and COL1A2the two genes encoding type I collagen. However, in the past years, remarkable advancements in bone research have expanded our understanding of the intricacies behind bone metabolism and identified novel molecular mechanisms contributing to skeletal health and disease. Especially high-throughput sequencing techniques have made family-based studies an efficient way to identify single genes causative of rare monogenic forms of osteoporosis and these have yielded several novel genes that encode proteins partaking in type I collagen modification or regulating bone cell function directly. New forms of monogenic osteoporosis, such as autosomal dominant osteoporosis caused by WNT1 mutations or X-linked osteoporosis due to PLS3 mutations, have revealed previously unidentified bone-regulating proteins and clarified specific roles of bone cells, expanded our understanding of possible inheritance mechanisms and paces of disease progression, and highlighted the potential of monogenic bone diseases to extend beyond the skeletal tissue.
Ich denke, dass Sie nicht recht sind. Es ich kann beweisen. Schreiben Sie mir in PM, wir werden umgehen.