Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
Zillikens MC., 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., 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 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 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-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.
AbstractLean 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.