Rask-Andersen, M. | Search bioRxiv

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↗

bioRxiv2017

Breastfeeding And Risk Of Asthma, Hay Fever And Eczema

BackgroundBreastfeeding is commonly proposed to protect against atopic diseases. However, studies aiming to quantify these protective effects have shown conflicting results.\n\nMethodsTo entrench the effects of breastfeeding on risk of asthma, hay fever and eczema, our study included a large study cohort, UK Biobank (N=502,682). Information was collected on whether participants had been breastfeed and on the prevalence of disease. Disease was tested for association with breastfeeding, adjusting or matching for influential covariates.\n\nFindingsA total of 443,068 participants were included in our analyses of which 71{middle dot}2% had been breastfed. The prevalence of asthma was 11{middle dot}4 % and 12{middle dot}7% in the breastfed and non-breastfed groups, and hay fever or eczema (23{middle dot}9% and 24{middle dot}8 % in the two groups respectively. When correcting or matching for potential confounders, we could not see any association between being breastfed and asthma. However, there were increased odds of hay fever and eczema among participants that had been breastfed (P=7{middle dot}78x10-6).\n\nInterpretationThis study reports that breastfeeding is associated with increased odds of hay fever and eczema but it show no evidence for breastfeeding being associated with asthma diagnosis.\n\nFundingThe Swedish Society for Medical Research (SSMF), the Kjell and Marta Beijers Foundation, Goran Gustafssons Foundation, the Swedish Medical Research Council (Project Number 2015-03327), the Marcus Borgstrom Foundation, the [A]ke Wiberg Foundation and the Vleugels Foundation.\n\nEvidence before this studyAtopic diseases affect quality of life for a large part of the human population and pose a very high socio-economic burden. Genetic, environmental, and a number of lifestyle factors influence our risk of developing atopic disorders and high familial prevalence is one of the strongest known risk factors for disease. Several environmental and lifestyle risk factors have already been well established in the scientific community, such as smoking on the risk of developing asthma. Breastfeeding is commonly argued to be protective against atopic diseases. However, studies aiming to quantify these protective effects have shown conflicting results.\n\nAdded value of this studyOur study is, to our knowledge, the largest investigation on how breastfeeding is associated with being diagnosed with asthma, hay fever and eczema at adult age. The study found breastfeeding to be associated with increased odds of being diagnosed with hay fever and eczema during life, while we found no association between breastfeeding and asthma. Our results for hay fever and eczema is in line with the western world hygiene hypothesis, but contradict the general picture of breastfeeding being protective.\n\nImplications of all the available evidenceTo be able to give parents correct advice on lifestyles choices that will protect their kids against atopic diseases, we need to clarify the currently conflicting results on the effect of breastfeeding on risk of atopic diseases. However, these results should not be used to recommend breastfeeding or to discourage it since the present study only investigates the association between breastfeeding history and being diagnosed with asthma, hay fever and eczema during lifetime.\n\nAbbreviations

epidemiology↗