Enhanced fracture risk prediction: a novel multi-trait genetic approach integrating polygenic scores of fracture-related traits

Sözen T, Özışık L, Başaran NÇ (2017) An overview and management of osteoporosis. Eur J Rheumatol 4:46–56. https://doi.org/10.5152/eurjrheum.2016.048

Article  PubMed  Google Scholar 

Nazrun AS, Tzar MN, Mokhtar SA, Mohamed IN (2014) A systematic review of the outcomes of osteoporotic fracture patients after hospital discharge: morbidity, subsequent fractures, and mortality. Ther Clin Risk Manag 10:937–948. https://doi.org/10.2147/TCRM.S72456

Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526. https://doi.org/10.1002/jbmr.2269

Article  PubMed  Google Scholar 

Singer A, Exuzides A, Spangler L, O’Malley C, Colby C, Johnston K, Agodoa I, Baker J, Kagan R (2015) Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin Proc 90:53–62. https://doi.org/10.1016/j.mayocp.2014.09.011

Article  PubMed  Google Scholar 

Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38:4. https://doi.org/10.1016/j.bone.2005.11.024

Article  Google Scholar 

Sigurdsson G, Halldorsson BV, Styrkarsdottir U, Kristjansson K, Stefansson K (2008) Impact of genetics on low bone mass in adults. J Bone Miner Res 23:1584–1590. https://doi.org/10.1359/jbmr.080507

Article  PubMed  Google Scholar 

Zhu X, Bai W, Zheng H (2021) Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications. Bone Research 9:23. https://doi.org/10.1038/s41413-021-00143-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nethander M, Movérare-Skrtic S, Kämpe A, Coward E, Reimann E, Grahnemo L, Borbély É, Helyes Z, Funck-Brentano T, Cohen-Solal M, Tuukkanen J, Koskela A, Wu J, Li L, Lu T, Gabrielsen ME, Estonian Biobank Research Team, Mägi R, Hoff M, Lerner UH, Henning P, Ullum H, Erikstrup C, Brunak S, Genomic Consortium DBDS, Langhammer A, Tuomi T, Oddsson A, Stefansson K, Pettersson-Kymmer U, Ostrowski SR, Pedersen OBV, Styrkarsdottir U, Mäkitie O, Hveem K, Richards JB, Ohlsson C (2023) An atlas of genetic determinants of forearm fracture. Nat Genet 55:1820-30. https://doi.org/10.1038/s41588-023-01527-3

Matteini AM, Tanaka T, Karasik D, Atzmon G, Chou WC, Eicher JD, Johnson AD, Arnold AM, Callisaya ML, Davies G, Evans DS, Holtfreter B, Lohman K, Lunetta KL, Mangino M, Smith AV, Smith JA, Teumer A, Yu L, Arking DE, Buchman AS, Chibinik LB, De Jager PL, Evans DA, Faul JD, Garcia ME, Gillham-Nasenya I, Gudnason V, Hofman A, Hsu YH, Ittermann T, Lahousse L, Liewald DC, Liu Y, Lopez L, Rivadeneira F, Rotter JI, Siggeirsdottir K, Starr JM, Thomson R, Tranah GJ, Uitterlinden AG, Völker U, Völzke H, Weir DR, Yaffe K, Zhao W, Zhuang WV, Zmuda JM, Bennett DA, Cummings SR, Deary IJ, Ferrucci L, Harris TB, Kardia SL, Kocher T, Kritchevsky SB, Psaty BM, Seshadri S, Spector TD, Srikanth VK, Windham BG, Zillikens MC, Newman AB, Walston JD, Kiel DP, Murabito JM (2016) GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell 15:792–800. https://doi.org/10.1111/acel.12468

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zillikens MC, Demissie S, Hsu Y, Yerges-Armstrong L, Chou W, Stolk L, Livshits G, Broer L, Johnson T, Koller DL, Kutalik Z, Luan J, Malkin I, Ried JS, Smith AV, Thorleifsson G, Vandenput L, Hua Zhao J, Zhang W, Aghdassi A, Åkesson K, Amin N, Baier LJ, Barroso I, Bennett DA, Bertram L, Biffar R, Bochud M, Boehnke M, Borecki IB, Buchman AS, Byberg L, Campbell H, Campos Obanda N, Cauley JA, Cawthon PM, Cederberg H, Chen Z, Cho NH, Jin Choi H, Claussnitzer M, Collins F, Cummings SR, De Jager PL, Demuth I, Dhonukshe-Rutten R, Diatchenko L, Eiriksdottir G, Enneman AW, Erdos M, Eriksson JG, Eriksson J, Estrada K, Evans DS, Feitosa MF, Fu M, Garcia M, Gieger C, Girke T, Glazer NL, Grallert H, Grewal J, Han B, Hanson RL, Hayward C, Hofman A, Hoffman EP, Homuth G, Hsueh W, Hubal MJ, Hubbard A, Huffman KM, Husted LB, Illig T, Ingelsson E, Ittermann T, Jansson J, Jordan JM, Jula A, Karlsson M, Khaw K, Kilpeläinen TO, Klopp N, Kloth JSL, Koistinen HA, Kraus WE, Kritchevsky S, Kuulasmaa T, Kuusisto J, Laakso M, Lahti J, Lang T, Langdahl BL, Launer LJ, Lee J, Lerch MM, Lewis JR, Lind L, Lindgren C, Liu Y, Liu T, Liu Y, Ljunggren Ö, Lorentzon M, Luben RN, Maixner W, McGuigan FE, Medina-Gomez C, Meitinger T, Melhus H, Mellström D, Melov S, Michaëlsson K, Mitchell BD, Morris AP, Mosekilde L, Newman A, Nielson CM, O’Connell JR, Oostra BA, Orwoll ES, Palotie A, Parker SCJ, Peacock M, Perola M, Peters A, Polasek O, Prince RL, Räikkönen K, Ralston SH, Ripatti S, Robbins JA, Rotter JI, Rudan I, Salomaa V, Satterfield S, Schadt EE, Schipf S, Scott L, Sehmi J, Shen J, Soo Shin C, Sigurdsson G, Smith S, Soranzo N, Stančáková A, Steinhagen-Thiessen E, Streeten EA, Styrkarsdottir U, Swart KMA, Tan S, Tarnopolsky MA, Thompson P, Thomson CA, Thorsteinsdottir U, Tikkanen E, Tranah GJ, Tuomilehto J, van Schoor NM, Verma A, Vollenweider P, Völzke H, Wactawski-Wende J, Walker M, Weedon MN, Welch R, Wichmann H, Widen E, Williams FMK, Wilson JF, Wright NC, Xie W, Yu L, Zhou Y, Chambers JC, Döring A, van Duijn CM, Econs MJ, Gudnason V, Kooner JS, Psaty BM, Spector TD, Stefansson K, Rivadeneira F, Uitterlinden AG, Wareham NJ, Ossowski V, Waterworth D, Loos RJF, Karasik D, Harris TB, Ohlsson C, Kiel DP (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80. https://doi.org/10.1038/s41467-017-00031-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang X, O’Reilly PF, Aschard H, Hsu YH, Richards JB, Dupuis J, Ingelsson E, Karasik D, Pilz S, Berry D, Kestenbaum B, Zheng J, Luan J, Sofianopoulou E, Streeten EA, Albanes D, Lutsey PL, Yao L, Tang W, Econs MJ, Wallaschofski H, Völzke H, Zhou A, Power C, McCarthy MI, Michos ED, Boerwinkle E, Weinstein SJ, Freedman ND, Huang WY, Van Schoor NM, van der Velde N, Groot LCPGM, Enneman A, Cupples LA, Booth SL, Vasan RS, Liu CT, Zhou Y, Ripatti S, Ohlsson C, Vandenput L, Lorentzon M, Eriksson JG, Shea MK, Houston DK, Kritchevsky SB, Liu Y, Lohman KK, Ferrucci L, Peacock M, Gieger C, Beekman M, Slagboom E, Deelen J, Heemst DV, Kleber ME, März W, de Boer IH, Wood AC, Rotter JI, Rich SS, Robinson-Cohen C, den Heijer M, Jarvelin MR, Cavadino A, Joshi PK, Wilson JF, Hayward C, Lind L, Michaëlsson K, Trompet S, Zillikens MC, Uitterlinden AG, Rivadeneira F, Broer L, Zgaga L, Campbell H, Theodoratou E, Farrington SM, Timofeeva M, Dunlop MG, Valdes AM, Tikkanen E, Lehtimäki T, Lyytikäinen LP, Kähönen M, Raitakari OT, Mikkilä V, Ikram MA, Sattar N, Jukema JW, Wareham NJ, Langenberg C, Forouhi NG, Gundersen TE, Khaw KT, Butterworth AS, Danesh J, Spector T, Wang TJ, Hyppönen E, Kraft P, Kiel DP (2018) Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun 9:260–262. https://doi.org/10.1038/s41467-017-02662-2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group Osteoporos Int 4:368–381. https://doi.org/10.1007/BF01622200

Article  CAS  Google Scholar 

Ho-Le TP, Center JR, Eisman JA, Nguyen HT, Nguyen TV (2017) Prediction of bone mineral density and fragility fracture by genetic profiling. J Bone Miner Res 32:285–293. https://doi.org/10.1002/jbmr.2998

Article  CAS  PubMed  Google Scholar 

Mitchell JA, Chesi A, Elci O, McCormack SE, Roy SM, Kalkwarf HJ, Lappe JM, Gilsanz V, Oberfield SE, Shepherd JA, Kelly A, Grant SF, Zemel BS (2016) Genetic risk scores implicated in adult bone fragility associate with pediatric bone density. J Bone Miner Res 31:789–795. https://doi.org/10.1002/jbmr.2744

Article  CAS  PubMed  Google Scholar 

Lu T, Forgetta V, Keller-Baruch J, Nethander M, Bennett D, Forest M, Bhatnagar S, Walters RG, Lin K, Chen Z, Li L, Karlsson M, Mellström D, Orwoll E, McCloskey EV, Kanis JA, Leslie WD, Clarke RJ, Ohlsson C, Greenwood CMT, Richards JB (2021) Improved prediction of fracture risk leveraging a genome-wide polygenic risk score. Genome Medicine 13:16. https://doi.org/10.1186/s13073-021-00838-6

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiao X, Wu Q (2021) The utility of genetic risk score to improve performance of FRAX for fracture prediction in US postmenopausal women. Calcif Tissue Int 108:746–756. https://doi.org/10.1007/s00223-021-00809-4

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee SH, Lee SW, Ahn SH, Kim T, Lim KH, Kim BJ, Cho EH, Kim SW, Kim TH, Kim GS, Kim SY, Koh JM, Kang C (2013) Multiple gene polymorphisms can improve prediction of nonvertebral fracture in postmenopausal women. J Bone Miner Res 28:2156–2164. https://doi.org/10.1002/jbmr.1955

Article  CAS  PubMed  Google Scholar 

Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, Dudbridge F, Lai FY, Kaptoge S, Brozynska M, Wang T, Ye S, Webb TR, Rutter MK, Tzoulaki I, Patel RS, Loos RJF, Keavney B, Hemingway H, Thompson J, Watkins H, Deloukas P, Di Angelantonio E, Butterworth AS, Danesh J, Samani NJ (2018) Genomic risk prediction of coronary artery disease in 480,000 adults: implications for primary prevention. J Am Coll Cardiol 72:1883–1893. https://doi.org/10.1016/j.jacc.2018.07.079

Article  PubMed  PubMed Central  Google Scholar 

Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M (2019) Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke. Nat Commun 10:5819. https://doi.org/10.1038/s41467-019-13848-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen X, Liu C, Si S, Li Y, Li W, Yuan T, Xue F (2021) Genomic risk score provides predictive performance for type 2 diabetes in the UK biobank. Acta Diabetol 58:467–474. https://doi.org/10.1007/s00592-020-01650-1

Article  CAS  PubMed  Google Scholar 

Läll K, Lepamets M, Palover M, Esko T, Metspalu A, Tõnisson N, Padrik P, Mägi R, Fischer K (2019) Polygenic prediction of breast cancer: comparison of genetic predictors and implications for risk stratification. BMC Cancer 19:557–561. https://doi.org/10.1186/s12885-019-5783-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clifford J. Rosen The epidemiology and pathogenesis of osteoporosis

Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397. https://doi.org/10.1007/s00198-007-0543-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, Liu B, Matthews P, Ong G, Pell J, Si

Comments (0)

No login
gif