@article {8538,
	title = {{Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects},
	journal = {Am J Hum Genet},
	volume = {102},
	year = {2018},
	month = {01},
	pages = {88{\textendash}102},
	abstract = {Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10\% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.},
	author = {Medina-Gomez, C. and Kemp, J. P. and Trajanoska, K. and Luan, J. and Chesi, A. and Ahluwalia, T. S. and Mook-Kanamori, D. O. and Ham, A. and Hartwig, F. P. and Evans, D. S. and Joro, R. and Nedeljkovic, I. and Zheng, H. F. and Zhu, K. and Atalay, M. and Liu, C. T. and Nethander, M. and Broer, L. and Porleifsson, G. and Mullin, B. H. and Handelman, S. K. and Nalls, M. A. and Jessen, L. E. and Heppe, D. H. M. and Richards, J. B. and Wang, C. and Chawes, B. and Schraut, K. E. and Amin, N. and Wareham, N. and Karasik, D. and Van der Velde, N. and Ikram, M. A. and Zemel, B. S. and Zhou, Y. and Carlsson, C. J. and Liu, Y. and McGuigan, F. E. and Boer, C. G. and B?nnelykke, K. and Ralston, S. H. and Robbins, J. A. and Walsh, J. P. and Zillikens, M. C. and Langenberg, C. and Li-Gao, R. and Williams, F. M. K. and Harris, T. B. and Akesson, K. and Jackson, R. D. and Sigurdsson, G. and den Heijer, M. and van der Eerden, B. C. J. and van de Peppel, J. and Spector, T. D. and Pennell, C. and Horta, B. L. and Felix, J. F. and Zhao, J. H. and Wilson, S. G. and de Mutsert, R. and Bisgaard, H. and Styrk?rsd?ttir, U. and Jaddoe, V. W. and Orwoll, E. and Lakka, T. A. and Scott, R. and Grant, S. F. A. and Lorentzon, M. and van Duijn, C. M. and Wilson, J. F. and Stefansson, K. and Psaty, B. M. and Kiel, D. P. and Ohlsson, C. and Ntzani, E. and van Wijnen, A. J. and Forgetta, V. and Ghanbari, M. and Logan, J. G. and Williams, G. R. and Bassett, J. H. D. and Croucher, P. I. and Evangelou, E. and Uitterlinden, A. G. and Ackert-Bicknell, C. L. and Tobias, J. H. and Evans, D. M. and Rivadeneira, F.}
}
@article {9310,
	title = {{A meta-analysis of genome-wide association studies identifies multiple longevity genes},
	journal = {Nat Commun},
	volume = {10},
	year = {2019},
	month = {Aug},
	pages = {3669},
	abstract = {2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.},
	author = {Deelen, J. and Evans, D. S. and Arking, D. E. and Tesi, N. and Nygaard, M. and Liu, X. and Wojczynski, M. K. and Biggs, M. L. and van der Spek, A. and Atzmon, G. and Ware, E. B. and Sarnowski, C. and Smith, A. V. and {\"a}, I. and Cordell, H. J. and Dose, J. and Amin, N. and Arnold, A. M. and Ayers, K. L. and Barzilai, N. and Becker, E. J. and Beekman, M. and {\'e}, H. and Christensen, K. and Christiansen, L. and Collerton, J. C. and Cubaynes, S. and Cummings, S. R. and Davies, K. and Debrabant, B. and Deleuze, J. F. and Duncan, R. and Faul, J. D. and Franceschi, C. and Galan, P. and Gudnason, V. and Harris, T. B. and Huisman, M. and Hurme, M. A. and Jagger, C. and Jansen, I. and {\"a}, M. and nen, M. and Karasik, D. and Kardia, S. L. R. and Kingston, A. and Kirkwood, T. B. L. and Launer, L. J. and ki, T. and Lieb, W. and inen, L. P. and Martin-Ruiz, C. and Min, J. and Nebel, A. and Newman, A. B. and Nie, C. and Nohr, E. A. and Orwoll, E. S. and Perls, T. T. and Province, M. A. and Psaty, B. M. and Raitakari, O. T. and Reinders, M. J. T. and Robine, J. M. and Rotter, J. I. and Sebastiani, P. and Smith, J. and rensen, T. I. A. and Taylor, K. D. and Uitterlinden, A. G. and van der Flier, W. and van der Lee, S. J. and van Duijn, C. M. and van Heemst, D. and Vaupel, J. W. and Weir, D. and Ye, K. and Zeng, Y. and Zheng, W. and Holstege, H. and Kiel, D. P. and Lunetta, K. L. and Slagboom, P. E. and Murabito, J. M.}
}
@article {8510,
	title = {{A meta-analysis of genome-wide association studies identifies multiple longevity genes},
	journal = {Nat Commun},
	volume = {10},
	year = {2019},
	month = {08},
	pages = {3669},
	abstract = {Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) {\^I}{\textmu}4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE {\^I}{\textmu}2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.},
	author = {Deelen, J. and Evans, D. S. and Arking, D. E. and Tesi, N. and Nygaard, M. and Liu, X. and Wojczynski, M. K. and Biggs, M. L. and van der Spek, A. and Atzmon, G. and Ware, E. B. and Sarnowski, C. and Smith, A. V. and Sepp?l?, I. and Cordell, H. J. and Dose, J. and Amin, N. and Arnold, A. M. and Ayers, K. L. and Barzilai, N. and Becker, E. J. and Beekman, M. and Blanch?, H. and Christensen, K. and Christiansen, L. and Collerton, J. C. and Cubaynes, S. and Cummings, S. R. and Davies, K. and Debrabant, B. and Deleuze, J. F. and Duncan, R. and Faul, J. D. and Franceschi, C. and Galan, P. and Gudnason, V. and Harris, T. B. and Huisman, M. and Hurme, M. A. and Jagger, C. and Jansen, I. and Jylh?, M. and K?h?nen, M. and Karasik, D. and Kardia, S. L. R. and Kingston, A. and Kirkwood, T. B. L. and Launer, L. J. and Lehtim?ki, T. and Lieb, W. and Lyytik?inen, L. P. and Martin-Ruiz, C. and Min, J. and Nebel, A. and Newman, A. B. and Nie, C. and Nohr, E. A. and Orwoll, E. S. and Perls, T. T. and Province, M. A. and Psaty, B. M. and Raitakari, O. T. and Reinders, M. J. T. and Robine, J. M. and Rotter, J. I. and Sebastiani, P. and Smith, J. and S?rensen, T. I. A. and Taylor, K. D. and Uitterlinden, A. G. and van der Flier, W. and van der Lee, S. J. and van Duijn, C. M. and van Heemst, D. and Vaupel, J. W. and Weir, D. and Ye, K. and Zeng, Y. and Zheng, W. and Holstege, H. and Kiel, D. P. and Lunetta, K. L. and Slagboom, P. E. and Murabito, J. M.}
}
@article {8517,
	title = {{Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry},
	journal = {J Bone Miner Res},
	volume = {34},
	year = {2019},
	month = {07},
	pages = {1284{\textendash}1296},
	abstract = {Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with {\^a}{\textasciicircum}{\textonequarter}2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p {\^a}{\textperthousand}¤ 2.6 {\~A}{\textemdash} 10-8 ) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 {\~A}{\textemdash} 10-5 ). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12\% to 22\% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. {\^A}{\textcopyright} 2019 American Society for Bone and Mineral Research.},
	author = {Hsu, Y. H. and Estrada, K. and Evangelou, E. and Ackert-Bicknell, C. and Akesson, K. and Beck, T. and Brown, S. J. and Capellini, T. and Carbone, L. and Cauley, J. and Cheung, C. L. and Cummings, S. R. and Czerwinski, S. and Demissie, S. and Econs, M. and Evans, D. and Farber, C. and Gautvik, K. and Harris, T. and Kammerer, C. and Kemp, J. and Koller, D. L. and Kung, A. and Lawlor, D. and Lee, M. and Lorentzon, M. and McGuigan, F. and Medina-Gomez, C. and Mitchell, B. and Newman, A. and Nielson, C. and Ohlsson, C. and Peacock, M. and Reppe, S. and Richards, J. B. and Robbins, J. and Sigurdsson, G. and Spector, T. D. and Stefansson, K. and Streeten, E. and Styrkarsdottir, U. and Tobias, J. and Trajanoska, K. and Uitterlinden, A. and Vandenput, L. and Wilson, S. G. and Yerges-Armstrong, L. and Young, M. and Zillikens, M. C. and Rivadeneira, F. and Kiel, D. P. and Karasik, D.}
}
@article {8660,
	title = {{Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women},
	journal = {Nat Commun},
	volume = {12},
	year = {2021},
	month = {01},
	pages = {654},
	abstract = {Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9\% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 {\texttimes} 10-17), arthritis (GDF5 p = 4 {\texttimes} 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.},
	author = {Jones, G. and Trajanoska, K. and Santanasto, A. J. and Stringa, N. and Kuo, C. L. and Atkins, J. L. and Lewis, J. R. and Duong, T. and Hong, S. and Biggs, M. L. and Luan, J. and Sarnowski, C. and Lunetta, K. L. and Tanaka, T. and Wojczynski, M. K. and Cvejkus, R. and Nethander, M. and Ghasemi, S. and Yang, J. and Zillikens, M. C. and Walter, S. and Sicinski, K. and Kague, E. and Ackert-Bicknell, C. L. and Arking, D. E. and Windham, B. G. and Boerwinkle, E. and Grove, M. L. and Graff, M. and Spira, D. and Demuth, I. and Van der Velde, N. and de Groot, L. C. P. G. M. and Psaty, B. M. and Odden, M. C. and Fohner, A. E. and Langenberg, C. and Wareham, N. J. and Bandinelli, S. and van Schoor, N. M. and Huisman, M. and Tan, Q. and Zmuda, J. and Mellstr{\"o}m, D. and Karlsson, M. and Bennett, D. A. and Buchman, A. S. and De Jager, P. L. and Uitterlinden, A. G. and V{\"o}lker, U. and Kocher, T. and Teumer, A. and Rodrigu{\'e}z-Ma{\~n}as, L. and Garc{\'\i}a, F. J. and Carnicero, J. A. and Herd, P. and Bertram, L. and Ohlsson, C. and Murabito, J. M. and Melzer, D. and Kuchel, G. A. and Ferrucci, L. and Karasik, D. and Rivadeneira, F. and Kiel, D. P. and Pilling, L. C.}
}
