Disentangling the genetics of lean mass.

Authors:
David Karasik M Carola Zillikens Yi-Hsiang Hsu Ali Aghdassi Kristina Akesson Najaf Amin Inês Barroso David A Bennett Lars Bertram Murielle Bochud Ingrid B Borecki Linda Broer Aron S Buchman Liisa Byberg Harry Campbell Natalia Campos-Obando Jane A Cauley Peggy M Cawthon John C Chambers Zhao Chen Nam H Cho Hyung Jin Choi Wen-Chi Chou Steven R Cummings Lisette C P G M de Groot Phillip L De Jager Ilja Demuth Luda Diatchenko Michael J Econs Gudny Eiriksdottir Anke W Enneman Joel Eriksson Johan G Eriksson Karol Estrada Daniel S Evans Mary F Feitosa Mao Fu Christian Gieger Harald Grallert Vilmundur Gudnason Launer J Lenore Caroline Hayward Albert Hofman Georg Homuth Kim M Huffman Lise B Husted Thomas Illig Erik Ingelsson Till Ittermann John-Olov Jansson Toby Johnson Reiner Biffar Joanne M Jordan Antti Jula Magnus Karlsson Kay-Tee Khaw Tuomas O Kilpeläinen Norman Klopp Jacqueline S L Kloth Daniel L Koller Jaspal S Kooner William E Kraus Stephen Kritchevsky Zoltán Kutalik Teemu Kuulasmaa Johanna Kuusisto Markku Laakso Jari Lahti Thomas Lang Bente L Langdahl Markus M Lerch Joshua R Lewis Christina Lill Lars Lind Cecilia Lindgren Yongmei Liu Gregory Livshits Östen Ljunggren Ruth J F Loos Mattias Lorentzon Jian'an Luan Robert N Luben Ida Malkin Fiona E McGuigan Carolina Medina-Gomez Thomas Meitinger Håkan Melhus Dan Mellström Karl Michaëlsson Braxton D Mitchell Andrew P Morris Leif Mosekilde Maria Nethander Anne B Newman Jeffery R O'Connell Ben A Oostra Eric S Orwoll Aarno Palotie Munro Peacock Markus Perola Annette Peters Richard L Prince Bruce M Psaty Katri Räikkönen Stuart H Ralston Samuli Ripatti Fernando Rivadeneira John A Robbins Jerome I Rotter Igor Rudan Veikko Salomaa Suzanne Satterfield Sabine Schipf Chan Soo Shin Albert V Smith Shad B Smith Nicole Soranzo Timothy D Spector Alena Stancáková Kari Stefansson Elisabeth Steinhagen-Thiessen Lisette Stolk Elizabeth A Streeten Unnur Styrkarsdottir Karin M A Swart Patricia Thompson Cynthia A Thomson Gudmar Thorleifsson Unnur Thorsteinsdottir Emmi Tikkanen Gregory J Tranah André G Uitterlinden Cornelia M van Duijn Natasja M van Schoor Liesbeth Vandenput Peter Vollenweider Henry Völzke Jean Wactawski-Wende Mark Walker Nicholas J Wareham Dawn Waterworth Michael N Weedon H-Erich Wichmann Elisabeth Widen Frances M K Williams James F Wilson Nicole C Wright Laura M Yerges-Armstrong Lei Yu Weihua Zhang Jing Hua Zhao Yanhua Zhou Carrie M Nielson Tamara B Harris Serkalem Demissie Douglas P Kiel Claes Ohlsson

Am J Clin Nutr 2019 02;109(2):276-287

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.

Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.

Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).

Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.

Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqy272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500901PMC
February 2019
40 Reads
6.770 Impact Factor

Publication Analysis

Top Keywords

fat mass
28
lean mass
16
mass
13
loci associated
12
fat
9
increasing alleles
8
model adjustment
8
adjustment fat
8
mass adjustments
8
mass fat
8
novel locus
8
locus tnrc6b
8
loci
8
alleles snps
8
genome-wide association
8
"body builder"
8
body mass
8
builder" loci
8
model
5
lean
5

Similar Publications