Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes

Is a diet low in greenhouse gas emissions a nutritious diet? - Analyses of self-selected diets in the LifeGene study

Background: Climate change is an urgent global issue and the food sector is a major contributor to greenhouse gas emissions (GHGE). Here we study if a diet low in GHGE could be a nutritious diet compared to the Nordic Nutrition Recommendations (NNR). Methods: The environmental impact of foods from Life Cycle Assessment (LCA) data was linked to a food frequency questionnaire (FFQ) filled out by 5,364 participants in the Swedish LifeGene study. Thereafter, we calculated the daily emission of CO2 equivalents (CO2e) as well as the intake of selected nutrients associated with vegetables, fruits, meat and dairy products. The CO2e was divided into quartiles were quartile 1 corresponds to a diet generating the lowest CO2e, and quartile 4 corresponds to a diet with the highest CO2e. Results: The overall diet-related emission was 4.7kg CO2e/day and person, corresponding to 1.7 ton CO2e/year. In general, there were only small differences in nutrient intake between groups of varying levels of CO2e, regardless if the intake was analyzed as absolute intake, energy percent or as nutrient density. Moreover, adherence to NNR was high for the group with the lowest CO2e, except for saturated fat where the intake was higher than recommended for all CO2e groups. On the other hand, only the group with the lowest CO2e fulfilled recommended intake of fiber. However, none of the CO2e groups reached the recommended intake of folate and vitamin D. Conclusions: Here we show that a self-selected diet low in CO2e provides comparable intake of nutrients as a diet high in in CO2e