Disentangling the genetics of lean mass

Abstract

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, age 2 , 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 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.

Zebrafish models of sarcopenia

“…Large-scale GWAS consortia continue to discover muscle-related loci through amassing data from immense cohorts of consistently phenotyped people. For example, international consortia have published the largest GWAS meta-analyses of lean mass (Zillikens et al, 2017;Karasik et al, 2018) and hand grip strength (Matteini et al, 2016;Willems et al, 2017;Tikkanen et al, 2018) to date.…”

The Role of Genetic Variation of BMI, Body Composition, and Fat Distribution for Mental Traits and Disorders: A Look-Up and Mendelian Randomization Study

“…The most recent GWAS for anthropometric traits were all published in 2019 substantiating the rapidly evolving dissection of their polygenic basis: (a) for BMI, 941 near-independent genome-wide significant SNPs at 536 polygenic loci have been detected (Yengo et al, 2018). (b) A GWAS for whole-body lean body mass (LBM; adjusted for sex, age, and height with or without fat mass adjustments) revealed seven LBM loci (Karasik et al, 2019). Another very recent GWAS for the proportion of body fat distribution in arms, legs, and trunk on 362,499 individuals from the UK Biobank identified 98 independent loci, 29 of which had not previously been associated with anthropometric traits including BMI (Rask-Andersen et al, 2019).…”

Disentangling the Genetics of Sarcopenia: prioritization of NUDT3 and KLF5 as genes for lean mass and HLA-DQB1-AS1 for hand grip strength based on associated SNPs

“…Potential genes were obtained from the work of Zillikens [2], Karasik [1] for LM and for HG, Willems [3] and Tikkanen [10]. Genes provided by Karasik, Zillikens and Willems were graded as first tier genes, while genes provided by Tikkanen were graded as second tier genes.…”

“…The results of GWAS for lean mass (LM) and hand grip strength (HG) was published in studies by Karasik et al,. [1], Zilikens et al [2], Willems et al [3] and Tikkanen et al [4], in various large human populations. The summary of eQTL data was obtained by studies by Westra et.…”

“…Many diseases known to man originate from more than one genetic locus. A GWAS (genome-wide association study) of lean muscle mass (LM) or hand grip strength (HG) was done in the studies by Karasik et al [1], Zilikens et al [2], Willems et al [3] and Tikkanen et al [4], in various large human populations. Various sample GWAS plots for LM and HG are also provided at the author's webpage 3 (www.tinyurl.com/abinarain and then navigate to "Educational Stuffs").…”