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Meta-Analysis
. 2012;7(3):e31369.
doi: 10.1371/journal.pone.0031369. Epub 2012 Mar 29.

Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts

Vesna Boraska  1 , Aaron Day-Williams, Christopher S Franklin, Katherine S Elliott, Kalliope Panoutsopoulou, Ioanna Tachmazidou, Eva Albrecht, Stefania Bandinelli, Lawrence J Beilin, Murielle Bochud, Gemma Cadby, Florian Ernst, David M Evans, Caroline Hayward, Andrew A Hicks, Jennifer Huffman, Cornelia Huth, Alan L James, Norman Klopp, Ivana Kolcic, Zoltán Kutalik, Debbie A Lawlor, Arthur W Musk, Marina Pehlic, Craig E Pennell, John R B Perry, Annette Peters, Ozren Polasek, Beate St Pourcain, Susan M Ring, Erika Salvi, Sabine Schipf, Jan A Staessen, Alexander Teumer, Nicholas Timpson, Veronique Vitart, Nicole M Warrington, Hanieh Yaghootkar, Tatijana Zemunik, Lina Zgaga, Ping An, Verneri Anttila, Ingrid B Borecki, Jostein Holmen, Ioanna Ntalla, Aarno Palotie, Kirsi H Pietiläinen, Juho Wedenoja, Bendik S Winsvold, George V Dedoussis, Jaakko Kaprio, Michael A Province, John-Anker Zwart, Michel Burnier, Harry Campbell, Daniele Cusi, George Davey Smith, Timothy M Frayling, Christian Gieger, Lyle J Palmer, Peter P Pramstaller, Igor Rudan, Henry Völzke, H-Erich Wichmann, Alan F Wright, Eleftheria Zeggini
Affiliations
Meta-Analysis

Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts

Vesna Boraska et al. PLoS One. 2012.

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.

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Conflict of interest statement

Competing Interests: The following commercial companies helped support this study: GlaxoSmithKline, Siemens Healthcare, Siemens AG, Novo Nordisk, Gyllenberg and Biomedicum Helsinki. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Study design. Each step includes non-overlapping, independent datasets.
Figure 2
Figure 2. Manhattan and QQ plots based on meta-analyses results of the discovery panel: a) combined set - age adjusted, b) combined set - age and BMI adjusted.
See this image and copyright information in PMC

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