Abstract
Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.
Highlights
Brachial circumference (BC) is a composite measure of muscle mass, skeletal size and fat tissue [1,2]
Analysis of anthropometric measures of peripheral fat distribution like BC could help in understanding complex phenotypes such as overweight and obesity that can lead to the development of chronic diseases, for example type 2 diabetes (T2D) and cardiovascular disease [4,5,6]
Genetic effects on fat distribution can be related to sex and in this study we aimed to evaluate sexspecific genetic associations with BC through analysis of men and women separately, as well as common associations through the analysis of a combined dataset
Summary
Brachial circumference (BC) is a composite measure of muscle mass, skeletal size and fat tissue [1,2]. Analysis of anthropometric measures of peripheral fat distribution like BC could help in understanding complex phenotypes such as overweight and obesity that can lead to the development of chronic diseases, for example type 2 diabetes (T2D) and cardiovascular disease [4,5,6]. Obesity in children can lead to development of chronic diseases such as hyperlipidaemia, hyperinsulinemia, hypertension, and early atherosclerosis later on in life [8]. Peripheral and overall fat distribution, assessed through body mass index (BMI), is partly modulated through different genetic effects [12]
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