Journal Article

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Döring, Angela, Broer, Linda, Räikkönen, Katri, Welch, Ryan, Ossowski, Vicky, Psaty, Bruce M., Robbins, John A., Tan, Sian-Tsung, Cederberg, Henna, Mitchell, Braxton D., Chen, Zhao, Mosekilde, Leif, Livshits, Gregory, Amin, Najaf, Stolk, Lisette, Wright, Nicole C., Baier, Leslie J., Eiriksdottir, Gudny, Ljunggren, Östen, Peters, Annette, Cauley, Jane A., Diatchenko, Luda, Husted, Lise B., Lerch, Markus M., Sigurdsson, Gunnar, Borecki, Ingrid B., Claussnitzer, Melina, Streeten, Elizabeth A., Campbell, Harry, Karlsson, Magnus, Barroso, Inês, Bochud, Murielle, Lindgren, Cecilia, Zillikens, M. Carola, Lind, Lars, Eriksson, Johan G., Smith, Shad, Thompson, Patricia, van Schoor, Natasja M., Chou, Wen-Chi, Feitosa, Mary F., Koistinen, Heikki A., Palotie, Aarno, Yu, Lei, Han, Bok-Ghee, Maixner, William, Zhou, Yanhua, Hsueh, Wen-Chi, Hubbard, Alan, Klopp, Norman, Wichmann, H.-Erich, Jordan, Joanne M., Buchman, Aron S., Åkesson, Kristina, Lorentzon, Mattias, Huffman, Kim M., Liu, Tian, Schadt, Eric E., Hanson, Robert L., Vandenput, Liesbeth, Hoffman, Eric P., Rivadeneira, Fernando, Lahti, Jari, Lang, Thomas, Salomaa, Vei

2017

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Portfolio
• Subject: 17-Hydroxysteroid Dehydrogenases - genetics / 631/208/199 / 631/208/205/2138 / 692/53/2423 / ADAMTS Proteins - genetics / Aldehyde Oxidoreductases - genetics / Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics / Basic Medicine / Body Composition / BONE-MINERAL DENSITY / CS Onderwijsinstituut / Extracellular Matrix Proteins - genetics / Gastroenterologi och hepatologi / Gastroenterology and Hepatology / GENE-EXPRESSION / Genome-Wide Association Study / HUMAN HEIGHT / Humanities and Social Sciences / Humans / Insulin Receptor Substrate Proteins - genetics / INSULIN-RESISTANCE / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / multidisciplinary / OBESITY / Onderwijsinstituut / Phenotype / PHYSICAL-DISABILITY / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Regulatory Elements, Transcriptional / SARCOPENIA / Science / Science (multidisciplinary) / SKELETAL-MUSCLE MASS / Thinness - genetics / UNITED-STATES / VARIANTS / Versicans - genetics