Ek, W. E. | bioRxiv Science

bioRxiv2017

Genome-wide association study of body fat distribution identifies novel loci and sex-specific effects

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested as more pathogenic compared to fat stored in other compartments of the body. In this study, we performed genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. A total of 97 loci, were identified to be associated with body fat distribution, 40 of which have not previously been associated with an anthropometric trait. A high degree of sex-heterogeneity was observed and associations were primarily observed in females, particularly for distribution of fat to the legs or trunk. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues a well as several enzymatically active members of the ADAMTS family of metalloproteinases, which are involved in extracellular matrix maintenance and remodeling.

genetics↗

bioRxiv2017

Genome-wide association analysis identifies 26 novel loci for asthma, hay fever and eczema

The disease risk for asthma, hay fever and eczema include both environmental and genetic risk factors and the comorbidity between the diseases are large. Heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors. In this GWAS, we include 346,545 Caucasian participants from the UK Biobank to increase power to identify novel loci for asthma, hay fever and eczema. We also investigate if associated lead SNPs have a significantly larger effect for one disease phenotype compared to the other phenotypes, to highlight possible disease specific effects.\n\nThis study identifies 141 loci, of which 41 are novel to this study, to be associated (P[≤]3x10-8) with asthma, hay fever or eczema, analysed separately or combined as a single phenotype. At four of the novel loci, TNFRSF8, MYRF, TSPAN8, and BHMG1, the lead SNPs were in LD (> 0.8) with potentially casual missense variants. For seven of the novel GWAS loci, the lead SNP was in LD (> 0.8) with genetic variants associated with gene expression (eQTL) where, for example, increased levels of TMEM258 as well as decreased levels of HHEX and ADAM19 was associated with decreased odds for asthma.\n\nOur study shows that a large amount of the genetic contribution to asthma, hay fever and eczema is shared between the diseases. Nonetheless, a number of SNPs have a significantly larger effect on one of the phenotypes suggesting that part of the genetic contribution is more phenotype specific.

genetics↗