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


ABSTRACT: 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.

SUBMITTER: Zillikens MC 

PROVIDER: S-EPMC5517526 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Zillikens M Carola MC   Demissie Serkalem S   Hsu Yi-Hsiang YH   Yerges-Armstrong Laura M LM   Chou Wen-Chi WC   Stolk Lisette L   Livshits Gregory G   Broer Linda L   Johnson Toby T   Koller Daniel L DL   Kutalik Zoltán Z   Luan Jian'an J   Malkin Ida I   Ried Janina S JS   Smith Albert V AV   Thorleifsson Gudmar G   Vandenput Liesbeth L   Hua Zhao Jing J   Zhang Weihua W   Aghdassi Ali A   Åkesson Kristina K   Amin Najaf N   Baier Leslie J LJ   Barroso Inês I   Bennett David A DA   Bertram Lars L   Biffar Rainer R   Bochud Murielle M   Boehnke Michael M   Borecki Ingrid B IB   Buchman Aron S AS   Byberg Liisa L   Campbell Harry H   Campos Obanda Natalia N   Cauley Jane A JA   Cawthon Peggy M PM   Cederberg Henna H   Chen Zhao Z   Cho Nam H NH   Jin Choi Hyung H   Claussnitzer Melina M   Collins Francis F   Cummings Steven R SR   De Jager Philip L PL   Demuth Ilja I   Dhonukshe-Rutten Rosalie A M RAM   Diatchenko Luda L   Eiriksdottir Gudny G   Enneman Anke W AW   Erdos Mike M   Eriksson Johan G JG   Eriksson Joel J   Estrada Karol K   Evans Daniel S DS   Feitosa Mary F MF   Fu Mao M   Garcia Melissa M   Gieger Christian C   Girke Thomas T   Glazer Nicole L NL   Grallert Harald H   Grewal Jagvir J   Han Bok-Ghee BG   Hanson Robert L RL   Hayward Caroline C   Hofman Albert A   Hoffman Eric P EP   Homuth Georg G   Hsueh Wen-Chi WC   Hubal Monica J MJ   Hubbard Alan A   Huffman Kim M KM   Husted Lise B LB   Illig Thomas T   Ingelsson Erik E   Ittermann Till T   Jansson John-Olov JO   Jordan Joanne M JM   Jula Antti A   Karlsson Magnus M   Khaw Kay-Tee KT   Kilpeläinen Tuomas O TO   Klopp Norman N   Kloth Jacqueline S L JSL   Koistinen Heikki A HA   Kraus William E WE   Kritchevsky Stephen S   Kuulasmaa Teemu T   Kuusisto Johanna J   Laakso Markku M   Lahti Jari J   Lang Thomas T   Langdahl Bente L BL   Launer Lenore J LJ   Lee Jong-Young JY   Lerch Markus M MM   Lewis Joshua R JR   Lind Lars L   Lindgren Cecilia C   Liu Yongmei Y   Liu Tian T   Liu Youfang Y   Ljunggren Östen Ö   Lorentzon Mattias M   Luben Robert N RN   Maixner William W   McGuigan Fiona E FE   Medina-Gomez Carolina C   Meitinger Thomas T   Melhus Håkan H   Mellström Dan D   Melov Simon S   Michaëlsson Karl K   Mitchell Braxton D BD   Morris Andrew P AP   Mosekilde Leif L   Newman Anne A   Nielson Carrie M CM   O'Connell Jeffrey R JR   Oostra Ben A BA   Orwoll Eric S ES   Palotie Aarno A   Parker Stephen C J SCJ   Peacock Munro M   Perola Markus M   Peters Annette A   Polasek Ozren O   Prince Richard L RL   Räikkönen Katri K   Ralston Stuart H SH   Ripatti Samuli S   Robbins John A JA   Rotter Jerome I JI   Rudan Igor I   Salomaa Veikko V   Satterfield Suzanne S   Schadt Eric E EE   Schipf Sabine S   Scott Laura L   Sehmi Joban J   Shen Jian J   Soo Shin Chan C   Sigurdsson Gunnar G   Smith Shad S   Soranzo Nicole N   Stančáková Alena A   Steinhagen-Thiessen Elisabeth E   Streeten Elizabeth A EA   Styrkarsdottir Unnur U   Swart Karin M A KMA   Tan Sian-Tsung ST   Tarnopolsky Mark A MA   Thompson Patricia P   Thomson Cynthia A CA   Thorsteinsdottir Unnur U   Tikkanen Emmi E   Tranah Gregory J GJ   Tuomilehto Jaakko J   van Schoor Natasja M NM   Verma Arjun A   Vollenweider Peter P   Völzke Henry H   Wactawski-Wende Jean J   Walker Mark M   Weedon Michael N MN   Welch Ryan R   Wichmann H-Erich HE   Widen Elisabeth E   Williams Frances M K FMK   Wilson James F JF   Wright Nicole C NC   Xie Weijia W   Yu Lei L   Zhou Yanhua Y   Chambers John C JC   Döring Angela A   van Duijn Cornelia M CM   Econs Michael J MJ   Gudnason Vilmundur V   Kooner Jaspal S JS   Psaty Bruce M BM   Spector Timothy D TD   Stefansson Kari K   Rivadeneira Fernando F   Uitterlinden André G AG   Wareham Nicholas J NJ   Ossowski Vicky V   Waterworth Dawn D   Loos Ruth J F RJF   Karasik David D   Harris Tamara B TB   Ohlsson Claes C   Kiel Douglas P DP  

Nature communications 20170719 1


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 (  ...[more]

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