Title | Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Zillikens, CM, Demissie, S, Hsu, Y-H, Yerges-Armstrong, LM, Chou, W-C, Stolk, L, Livshits, G, Broer, L, Johnson, T, Koller, DL, Kutalik, Z, Luan, J'an, Malkin, I, Ried, JS, Smith, AV, Thorleifsson, G, Vandenput, L, Zhao, JHua, 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, Obanda, NCampos, Cauley, JA, Cawthon, PM, Cederberg, H, Chen, Z, Cho, NH, Choi, HJin, Claussnitzer, M, Collins, F, Cummings, SR, De Jager, PL, Demuth, I, Dhonukshe-Rutten, RAM, 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-G, Hanson, RL, Hayward, C, Hofman, A, Hoffman, EP, Homuth, G, Hsueh, W-C, Hubal, MJ, Hubbard, A, Huffman, KM, Husted, LB, Illig, T, Ingelsson, E, Ittermann, T, Jansson, J-O, Jordan, JM, Jula, A, Karlsson, M, Khaw, K-T, 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-Y, Lerch, MM, Lewis, JR, Lind, L, Lindgren, C, Liu, Y, Liu, T, Liu, Y, Ljunggren, O, Lorentzon, M, Luben, RN, Maixner, W, McGuigan, FE, Medina-Gómez, 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, Shin, CSoo, Sigurdsson, G, Smith, S, Soranzo, N, Stančáková, A, Steinhagen-Thiessen, E, Streeten, EA, Styrkarsdottir, U, Swart, KMA, Tan, S-T, 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-E, 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 |
Journal | Nat Commun |
Volume | 8 |
Issue | 1 |
Pagination | 80 |
Date Published | 2017 Jul 19 |
ISSN | 2041-1723 |
Abstract | <p>Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.</p> |
DOI | 10.1038/s41467-017-00031-7 |
Alternate Journal | Nat Commun |
PubMed ID | 28724990 |
PubMed Central ID | PMC5517526 |
Grant List | UL1 RR033176 / RR / NCRR NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States R00 DK099240 / DK / NIDDK NIH HHS / United States P60 AR049465 / AR / NIAMS NIH HHS / United States R01 AR046838 / AR / NIAMS NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States R01 AG024480 / AG / NIA NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States P60 AR030701 / AR / NIAMS NIH HHS / United States UL1 TR000128 / TR / NCATS NIH HHS / United States R01 AR035583 / AR / NIAMS NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States ZIA HG000024 / HG / NHGRI NIH HHS / United States R01 AR035584 / AR / NIAMS NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States U01 AG042124 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U01 AG042145 / AG / NIA NIH HHS / United States R01 AG027576 / AG / NIA NIH HHS / United States R01 DK075681 / DK / NIDDK NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States R01 AG041517 / AG / NIA NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States M01 RR000750 / RR / NCRR NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States U01 HL084756 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States R01 AG005407 / AG / NIA NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States U01 AG042168 / AG / NIA NIH HHS / United States U01 AG042140 / AG / NIA NIH HHS / United States U01 HL072515 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States U24 AG051129 / AG / NIA NIH HHS / United States U01 DK062370 / DK / NIDDK NIH HHS / United States R01 AR057118 / AR / NIAMS NIH HHS / United States R01 HL088215 / HL / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States RC2 AR058973 / AR / NIAMS NIH HHS / United States R01 AR035582 / AR / NIAMS NIH HHS / United States / / Wellcome Trust / United Kingdom U01 AG027810 / AG / NIA NIH HHS / United States R01 AG005394 / AG / NIA NIH HHS / United States F32 AR059469 / AR / NIAMS NIH HHS / United States R01 HL117078 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 HL087700 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States U01 GM074518 / GM / NIGMS NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States U01 AG042143 / AG / NIA NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States U01 AG042139 / AG / NIA NIH HHS / United States R01 AG027574 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States U01 AR066160 / AR / NIAMS NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States |