8. Genetics of Osteoporosis in Older Age

Burger H, de Laet CE, van Daele PL, Weel AE, Witteman JC, Hofman A, Pols HA. Risk factors for increased bone loss in an elderly population: the Rotterdam Study. Am J Epidemiol. 1998;147:871–9.CrossRefPubMed

Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res. 2000;15:710–20.CrossRefPubMed

Melton 3rd LJ, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL. Determinants of bone loss from the femoral neck in women of different ages. J Bone Miner Res. 2000;15:24–31.CrossRefPubMed

Riggs BL, Khosla S, Melton LJ. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998;13:763–73.CrossRefPubMed

U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.

Schulze TG, McMahon FJ. Defining the phenotype in human genetic studies: forward genetics and reverse phenotyping. Hum Hered. 2004;58:131–8.CrossRefPubMed

Pan WH, Lynn KS, Chen CH, Wu YL, Lin CY, Chang HY. Using endophenotypes for pathway clusters to map complex disease genes. Genet Epidemiol. 2006;30:143–54.CrossRefPubMed

Kwan JS, Hsu YH, Cheung CL, Dupuis J, Saint-Pierre A, Eriksson J, Handelman SK, Aragaki A, Karasik D, Pramstaller PP, Kooperberg C, Lacroix AZ, Larson MG, Lau KS, Lorentzon M, Pichler I, Sham PC, Taliun D, Vandenput L, Kiel DP, Hicks AA, Jackson RD, Ohlsson C, Benjamin EJ, Kung AW. Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. Hum Mol Genet. 2014;23(24):6684–93.CrossRefPubMedPubMedCentral

Livshits G, Yakovenko C, Kobyliansky E. Quantitative genetic analysis of circulating levels of biochemical markers of bone formation. Am J Med Genet. 2000;94:324–31.CrossRefPubMed

Deng HW, Mahaney MC, Williams JT, Li J, Conway T, Davies KM, Li JL, Deng H, Recker RR. Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases. Genet Epidemiol. 2002;22:​12–25.CrossRefPubMed

Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Gennari L, Albagha O, Ralston SH, Tsatsoulis A. Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: a meta-analysis. J Bone Miner Res. 2002;17:2048–60.CrossRefPubMed

Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest. 2001;107:899–907.CrossRefPubMedPubMedCentral

Rivadeneira F, Houwing-Duistermaat JJ, Beck TJ, Janssen JA, Hofman A, Pols HA, Van Duijn CM, Uitterlinden AG. The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam study. J Bone Miner Res. 2004;19:1280–90.CrossRefPubMed

Rivadeneira F, Houwing-Duistermaat JJ, Vaessen N, Vergeer-Drop JM, Hofman A, Pols HA, Van Duijn CM, Uitterlinden AG. Association between an insulin-like growth factor I gene promoter polymorphism and bone mineral density in the elderly: the Rotterdam Study. J Clin Endocrinol Metab. 2003;88:3878–84.CrossRefPubMed

Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009;106:9362–7.CrossRefPubMedPubMedCentral

Sivakumaran S, Agakov F, Theodoratou E, Prendergast JG, Zgaga L, Manolio T, Rudan I, McKeigue P, Wilson JF, Campbell H. Abundant pleiotropy in human complex diseases and traits. Am J Hum Genet. 2011;89:607–18.CrossRefPubMedPubMedCentral

Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L, Parkinson H. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 2014;42:D1001–6.CrossRefPubMed

Zheng HF, Tobias JH, Duncan E, Evans DM, Eriksson J, Paternoster L, Yerges-Armstrong LM, Lehtimaki T, Bergstrom U, Kahonen M, Leo PJ, Raitakari O, Laaksonen M, Nicholson GC, Viikari J, Ladouceur M, Lyytikainen LP, Medina-Gomez C, Rivadeneira F, Prince RL, Sievanen H, Leslie WD, Mellstrom D, Eisman JA, Moverare-Skrtic S, Goltzman D, Hanley DA, Jones G, St Pourcain B, Xiao Y, Timpson NJ, Smith GD, Reid IR, Ring SM, Sambrook PN, Karlsson M, Dennison EM, Kemp JP, Danoy P, Sayers A, Wilson SG, Nethander M, McCloskey E, Vandenput L, Eastell R, Liu J, Spector T, Mitchell BD, Streeten EA, Brommage R, Pettersson-Kymmer U, Brown MA, Ohlsson C, Richards JB, Lorentzon M. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet. 2012;8:e1002745.CrossRefPubMedPubMedCentral

Koller DL, Zheng HF, Karasik D, Yerges-Armstrong L, Liu CT, McGuigan F, Kemp JP, Giroux S, Lai D, Edenberg HJ, Peacock M, Czerwinski SA, Choh AC, McMahon G, St Pourcain B, Timpson NJ, Lawlor DA, Evans DM, Towne B, Blangero J, Carless MA, Kammerer C, Goltzman D, Kovacs CS, Prior JC, Spector TD, Rousseau F, Tobias JH, Akesson K, Econs MJ, Mitchell BD, Richards JB, Kiel DP, Foroud T. Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women. J Bone Miner Res. 2013;28:547–58.CrossRefPubMedPubMedCentral

Karasik D, Hsu YH, Zhou Y, Cupples LA, Kiel DP, Demissie S. Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham study. J Bone Miner Res. 2010;25:1555–63.CrossRefPubMedPubMedCentral

Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OM, Amin N, Kemp JP, Koller DL, Li G, Liu CT, Minster RL, Moayyeri A, Vandenput L, Willner D, Xiao SM, Yerges-Armstrong LM, Zheng HF, Alonso N, Eriksson J, Kammerer CM, Kaptoge SK, Leo PJ, Thorleifsson G, Wilson SG, Wilson JF, Aalto V, Alen M, Aragaki AK, Aspelund T, Center JR, Dailiana Z, Duggan DJ, Garcia M, Garcia-Giralt N, Giroux S, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Khusainova R, Kim GS, Kooperberg C, Koromila T, Kruk M, Laaksonen M, Lacroix AZ, Lee SH, Leung PC, Lewis JR, Masi L, Mencej-Bedrac S, Nguyen TV, Nogues X, Patel MS, Prezelj J, Rose LM, Scollen S, Siggeirsdottir K, Smith AV, Svensson O, Trompet S, Trummer O, van Schoor NM, Woo J, Zhu K, Balcells S, Brandi ML, Buckley BM, Cheng S, Christiansen C, Cooper C, Dedoussis G, Ford I, Frost M, Goltzman D, Gonzalez-Macias J, Kahonen M, Karlsson M, Khusnutdinova E, Koh JM, Kollia P, Langdahl BL, Leslie WD, Lips P, Ljunggren O, Lorenc RS, Marc J, Mellstrom D, Obermayer-Pietsch B, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Ridker PM, Rousseau F, Lagboom PE, Tang NL, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44:491–501.CrossRefPubMedPubMedCentral

Moayyeri A, Hsu YH, Karasik D, Estrada K, Xiao SM, Nielson C, Srikanth P, Giroux S, Wilson SG, Zheng HF, Smith AV, Pye SR, Leo PJ, Teumer A, Hwang JY, Ohlsson C, McGuigan F, Minster RL, Hayward C, Olmos JM, Lyytikainen LP, Lewis JR, Swart KM, Masi L, Oldmeadow C, Holliday EG, Cheng S, van Schoor NM, Harvey NC, Kruk M, del Greco MF, Igl W, Trummer O, Grigoriou E, Luben R, Liu CT, Zhou Y, Oei L, Medina-Gomez C, Zmuda J, Tranah G, Brown SJ, Williams FM, Soranzo N, Jakobsdottir J, Siggeirsdottir K, Holliday KL, Hannemann A, Go MJ, Garcia M, Polasek O, Laaksonen M, Zhu K, Enneman AW, McEvoy M, Peel R, Sham PC, Jaworski M, Johansson A, Hicks AA, Pludowski P, Scott R, Dhonukshe-Rutten RA, van der Velde N, Kahonen M, Viikari JS, Sievanen H, Raitakari OT, Gonzalez-Macias J, Hernandez JL, Mellstrom D, Ljunggren O, Cho YS, Volker U, Nauck M, Homuth G, Volzke H, Haring R, Brown MA, McCloskey E, Nicholson GC, Eastell R, Eisman JA, Jones G, Reid IR, Dennison EM, Wark J, Boonen S, Vanderschueren D, Wu FC, Aspelund T, Richards JB, Bauer D, Hofman A, Khaw KT, Dedoussis G, Obermayer-Pietsch B, Gyllensten U, Pramstaller PP, Lorenc RS, et al. Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. Hum Mol Genet. 2014;23:3054–68.CrossRefPubMedPubMedCentral

Hwang JY, Lee SH, Go MJ, Kim BJ, Kou I, Ikegawa S, Guo Y, Deng HW, Raychaudhuri S, Kim YJ, Oh JH, Kim Y, Moon S, Kim DJ, Koo H, Cha MJ, Lee MH, Yun JY, Yoo HS, Kang YA, Cho EH, Kim SW, Oh KW, Kang MI, Son HY, Kim SY, Kim GS, Han BG, Cho YS, Cho MC, Lee JY, Koh JM. Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture. J Med Genet. 2013;50:212–9.CrossRefPubMedPubMedCentral

Guo Y, Tan LJ, Lei SF, Yang TL, Chen XD, Zhang F, Chen Y, Pan F, Yan H, Liu X, Tian Q, Zhang ZX, Zhou Q, Qiu C, Dong SS, Xu XH, Guo YF, Zhu XZ, Liu SL, Wang XL, Li X, Luo Y, Zhang LS, Li M, Wang JT, Wen T, Drees B, Hamilton J, Papasian CJ, Recker RR, Song XP, Cheng J, Deng HW. Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis. PLoS Genet. 2010;6:e1000806.CrossRefPubMedPubMedCentral

Luo L, Xia W, Nie M, Sun Y, Jiang Y, Zhao J, He S, Xu L. Association of ESR1 and C6orf97 gene polymorphism with osteoporosis in postmenopausal women. Mol Biol Rep. 2014;41:3235–43.CrossRefPubMed

Medina-Gomez C, Kemp JP, Estrada K, Eriksson J, Liu J, Reppe S, Evans DM, Heppe DH, Vandenput L, Herrera L, Ring SM, Kruithof CJ, Timpson NJ, Zillikens MC, Olstad OK, Zheng HF, Richards JB, St Pourcain B, Hofman A, Jaddoe VW, Smith GD, Lorentzon M, Gautvik KM, Uitterlinden AG, Brommage R, Ohlsson C, Tobias JH, Rivadeneira F. Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus. PLoS Genet. 2012;8:e1002718.CrossRefPubMedPubMedCentral

Liu YJ, Zhang L, Papasian CJ, Deng HW. Genome-wide association studies for osteoporosis: a 2013 update. J Bone Metab. 2014;21:99–116.CrossRefPubMedPubMedCentral

Oei L, Estrada K, Duncan EL, Christiansen C, Liu CT, Langdahl BL, Obermayer-Pietsch B, Riancho JA, Prince RL, van Schoor NM, McCloskey E, Hsu YH, Evangelou E, Ntzani E, Evans DM, Alonso N, Husted LB, Valero C, Hernandez JL, Lewis JR, Kaptoge SK, Zhu K, Cupples LA, Medina-Gomez C, Vandenput L, Kim GS, Hun Lee S, Castano-Betancourt MC, Oei EH, Martinez J, Daroszewska A, van der Klift M, Mellstrom D, Herrera L, Karlsson MK, Hofman A, Ljunggren O, Pols HA, Stolk L, van Meurs JB, Ioannidis JP, Zillikens MC, Lips P, Karasik D, Uitterlinden AG, Styrkarsdottir U, Brown MA, Koh JM, Richards JB, Reeve J, Ohlsson C, Ralston SH, Kiel DP, Rivadeneira F. Genome-wide association study for radiographic vertebral fractures: a potential role for the 16q24 BMD locus. Bone. 2014;59:20–7.CrossRefPubMedPubMedCentral

Oei L, Hsu YH, Styrkarsdottir U, Eussen BH, de Klein A, Peters MJ, Halldorsson B, Liu CT, Alonso N, Kaptoge SK, Thorleifsson G, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Kruk M, Lewis JR, Patel MS, Scollen S, Svensson O, Trompet S, van Schoor NM, Zhu K, Buckley BM, Cooper C, Ford I, Goltzman D, Gonzalez-Macias J, Langdahl BL, Leslie WD, Lips P, Lorenc RS, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Slagboom PE, Garcia-Ibarbia C, Ingvarsson T, Johannsdottir H, Luben R, Medina-Gomez C, Arp P, Nandakumar K, Palsson ST, Sigurdsson G, van Meurs JB, Zhou Y, Hofman A, Jukema JW, Pols HA, Prince RL, Cupples LA, Marshall CR, Pinto D, Sato D, Scherer SW, Reeve J, Thorsteinsdottir U, Karasik D, Richards JB, Stefansson K, Uitterlinden AG, Ralston SH, Ioannidis JP, Kiel DP, Rivadeneira F, Estrada K. A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus. J Med Genet. 2014;51:122–31.CrossRefPubMed

Hill CA, Sussan TE, Reeves RH, Richtsmeier JT. Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic “Down syndrome” mice. Am J Med Genet A. 2009;149A:2158–65.CrossRefPubMedPubMedCentral

Fox KM, Cummings SR, Powell-Threets K, Stone K. Family history and risk of osteoporotic fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1998;8:557–62.CrossRefPubMed

Liu CT, Estrada K, Yerges-Armstrong LM, Amin N, Evangelou E, Li G, Minster RL, Carless MA, Kammerer CM, Oei L, Zhou Y, Alonso N, Dailiana Z, Eriksson J, Garcia-Giralt N, Giroux S, Husted LB, Khusainova RI, Koromila T, Kung AW, Lewis JR, Masi L, Mencej-Bedrac S, Nogues X, Patel MS, Prezelj J, Richards JB, Sham PC, Spector T, Vandenput L, Xiao SM, Zheng HF, Zhu K, Balcells S, Brandi ML, Frost M, Goltzman D, Gonzalez-Macias J, Karlsson M, Khusnutdinova EK, Kollia P, Langdahl BL, Ljunggren O, Lorentzon M, Marc J, Mellstrom D, Ohlsson C, Olmos JM, Ralston SH, Riancho JA, Rousseau F, Urreizti R, Van Hul W, Zarrabeitia MT, Castano-Betancourt M, Demissie S, Grundberg E, Herrera L, Kwan T, Medina-Gomez C, Pastinen T, Sigurdsson G, Thorleifsson G, Vanmeurs JB, Blangero J, Hofman A, Liu Y, Mitchell BD, O’Connell JR, Oostra BA, Rotter JI, Stefansson K, Streeten EA, Styrkarsdottir U, Thorsteinsdottir U, Tylavsky FA, Uitterlinden A, Cauley JA, Harris TB, Ioannidis JP, Psaty BM, Robbins JA, Zillikens MC, Vanduijn CM, Prince RL, Karasik D, Rivadeneira F, Kiel DP, Cupples LA, Hsu YH. Assessment of gene-by-sex interaction effect on bone mineral density. J Bone Miner Res. 2012;27:2051–64.CrossRefPubMedPubMedCentral

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. 2003;1:E69.CrossRefPubMedPubMedCentral

Sonoda T, Takada J, Iba K, Asakura S, Yamashita T, Mori M. Interaction between ESRalpha polymorphisms and environmental factors in osteoporosis. J Orthop Res. 2012;30:1529–34.CrossRefPubMed

Eriksson J, Evans DS, Nielson CM, Shen J, Srikanth P, Hochberg M, McWeeney S, Cawthon PM, Wilmot B, Zmuda J, Tranah G, Mirel DB, Challa S, Mooney M, Crenshaw A, Karlsson M, Mellstrom D, Vandenput L, Orwoll E, Ohlsson C. Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects. J Bone Miner Res. 2014;30(1):184–94.CrossRef

Paternoster L, Lorentzon M, Lehtimaki T, Eriksson J, Kahonen M, Raitakari O, Laaksonen M, Sievanen H, Viikari J, Lyytikainen LP, Mellstrom D, Karlsson M, Ljunggren O, Grundberg E, Kemp JP, Sayers A, Nethander M, Evans DM, Vandenput L, Tobias JH, Ohlsson C. Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure. PLoS Genet. 2013;9:e1003247.CrossRefPubMedPubMedCentral

Richards JB, Zheng HF, Spector TD. Genetics of osteoporosis from genome-wide association studies: advances and challenges. Nat Rev Genet. 2012;13:576–88.CrossRefPubMed

Fenger M. Next generation genetics. Front Genet. 2014;5:322.CrossRefPubMedPubMedCentral

Ackert-Bicknell CL, Karasik D. Impact of the environment on the skeleton: is it modulated by genetic factors? Curr Osteoporos Rep. 2013;11(3):219–28.CrossRefPubMedPubMedCentral

Saarinen A, Mayranpaa MK, Lehesjoki AE, Makitie O. Low-density lipoprotein receptor-related protein 5 (LRP5) variation in fracture prone children. Bone. 2010;46:940–5.CrossRefPubMed

McGuigan F, Kumar J, Ivaska KK, Obrant KJ, Gerdhem P, Akesson K. Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification. J Bone Miner Res. 2010;25:1392–9.CrossRefPubMed

Koromila T, Georgoulias P, Dailiana Z, Ntzani EE, Samara S, Chassanidis C, Aleporou-Marinou V, Kollia P. CER1 gene variations associated with bone mineral density, bone markers, and early menopause in postmenopausal women. Hum Genomics. 2013;7:21.CrossRefPubMedPubMedCentral

Hendrickx G, Boudin E, Fijałkowski I, Nielsen TL, Andersen M, Brixen K, Van Hul W. Variation in the Kozak sequence of WNT16 results in an increased translation and is associated with osteoporosis related parameters. Bone. 2014;59:57–65.CrossRefPubMed

Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, Bergmann C, Rohrbach M, Koerber F, Zimmermann K, de Vries P, Wirth B, Schoenau E, Wollnik B, Veltman JA, Hoischen A, Netzer C. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011;88:362–71.CrossRefPubMedPubMedCentral

Fahiminiya S, Majewski J, Roughley P, Roschger P, Klaushofer K, Rauch F. Whole-exome sequencing reveals a heterozygous LRP5 mutation in a 6-year-old boy with vertebral compression fractures and low trabecular bone density. Bone. 2013;57:41–6.CrossRefPubMed

McInerney-Leo AM, Duncan EL, Leo PJ, Gardiner B, Bradbury LA, Harris JE, Clark GR, Brown MA, Zankl A. COL1A1 C-propeptide cleavage site mutation causes high bone mass, bone fragility and jaw lesions: a new cause of gnathodiaphyseal dysplasia? Clin Genet. 2014;88(1):49–55.CrossRefPubMed

Styrkarsdottir U, Thorleifsson G, Sulem P, Gudbjartsson DF, Sigurdsson A, Jonasdottir A, Oddsson A, Helgason A, Magnusson OT, Walters GB, Frigge ML, Helgadottir HT, Johannsdottir H, Bergsteinsdottir K, Ogmundsdottir MH, Center JR, Nguyen TV, Eisman JA, Christiansen C, Steingrimsson E, Jonasson JG, Tryggvadottir L, Eyjolfsson GI, Theodors A, Jonsson T, Ingvarsson T, Olafsson I, Rafnar T, Kong A, Sigurdsson G, Masson G, Thorsteinsdottir U, Stefansson K. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. Nature. 2013;497:517–20.CrossRefPubMed

Friedman E, Moran DS, Ben-Avraham D, Yanovich R, Atzmon G. Novel candidate genes putatively involved in stress fracture predisposition detected by whole-exome sequencing. Genet Res (Camb). 2014;96:e004.CrossRef

Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, Mccarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Moayyeri A, Mokry LE, Claussnitzer M, Cheung W, Cheng CH, Medina-Gomez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Gregson CL, Hibbs MA, Paquette D, Hofman A, Wibom C, Marshall M, Tranah GJ, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, De Groot LC, Van Schoor NM, Van Der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, Van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, Haessler J, Lacroix AZ, Chasman DI, Giulianini F, Rose LM, Eisman JA, Ridker PM, Nguyen TV, Nogues X, Center JR, Garcia-Giralt N, Gudnason V, Launer LL, Mellstrom D, Vandenput L, Amin N, Karlsson MK, Van Duijn CM, Ljunggren O, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussiere J, Arp PP, et al. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature. 2015;526(7571):112–7.

Pajala S, Era P, Koskenvuo M, Kaprio J, Viljanen A, Rantanen T. Genetic factors and susceptibility to falls in older women. J Am Geriatr Soc. 2006;54:613–8.CrossRefPubMed

Barr R, Macdonald H, Stewart A, McGuigan F, Rogers A, Eastell R, Felsenberg D, Gluer C, Roux C, Reid DM. Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS). Osteoporos Int. 2010;21:457–66.CrossRefPubMed

Onder G, Capoluongo E, Danese P, Settanni S, Russo A, Concolino P, Bernabei R, Landi F. Vitamin D receptor polymorphisms and falls among older adults living in the community: results from the ilSIRENTE study. J Bone Miner Res. 2008;23:1031–6.CrossRefPubMed

Dimitriou R, Carr IM, West RM, Markham AF, Giannoudis PV. Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway. BMC Musculoskelet Disord. 2011;12:44.CrossRefPubMedPubMedCentral

Guimarães JM, Guimarães ICDV, Duarte MEL, Vieira T, Vianna VF, Fernandes MBC, Vieira AR, Casado PL. Polymorphisms in BMP4 and FGFR1 genes are associated with fracture non-union. J Orthop Res. 2013;31:1971–9.CrossRefPubMed

Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem. 2003;88:873–84.CrossRefPubMed

Drissi H, Paglia DN, Alaee F, Yoshida R. Constructing the toolbox: patient-specific genetic factors of altered fracture healing. Genes Dis. 2014;1:140–8.CrossRefPubMedPubMedCentral

Cushman SA. Grand challenges in evolutionary and population genetics: the importance of integrating epigenetics, genomics, modeling, and experimentation. Front Genet. 2014;5:197.CrossRefPubMedPubMedCentral