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Canela-Xandri, O.

Publications and source records attributed to Canela-Xandri, O..

3 recordsLinked to original sources

The genetic architecture of hair colour in the UK population

We have extensively mapped the genes responsible for hair colour in the UK population. MC1R mutations are well established as the principal genetic cause of red hair colour, but with variable penetrance. We find variation at genes encoding its agonist (POMC), inverse agonist (ASIP) and other loci contribute to red hair and demonstrate epistasis between MC1R and some of these loci. Blonde hair is associated with over 200 loci, and we find a genetic continuum from black through dark and light brown to blonde. Many of the associated genes are involved in hair growth or texture, emphasising the cellular connections between keratinocytes and melanocytes in the determination of hair colour.

genetics

Indirect assortative mating for human disease and longevity

Phenotypic correlations of couples for phenotypes evident at the time of mate choice, like height, are well documented. Similarly, phenotypic correlations among partners for traits not directly observable at the time of mate choice, like longevity or late-onset disease status, have been reported. Partner correlations for longevity and late-onset disease are comparable in magnitude to correlations in 1st degree relatives. These correlations could arise as a consequence of convergence after mate choice, due to initial assortment on observable correlates of one or more risk factors (e.g. BMI), referred to as indirect assortative mating, or both. Using couples from the UK Biobank cohort, we show that longevity and disease history of the parents of white British couples is correlated. The correlations in parental longevity are replicated in the FamiLinx cohort. These correlations exceed what would be expected due to variations in lifespan based on year and location of birth. This suggests the presence of assortment on factors correlated with disease and lifespan, which show correlations across generations. Birth year, birth location, Townsend Deprivation Index, height, waist to hip ratio, BMI and smoking history of UK Biobank couples explained ~70% of the couple correlation in parental lifespan. For cardiovascular diseases, in particular hypertension, we find significant correlations in genetic values among partners, which support a model where partners assort for risk factors genetically correlated with cardiovascular disease. Identifying the factors that mediate indirect assortment on longevity and human disease risk will help to unravel what factors affect human disease and ultimately longevity.

genetics

An atlas of genetic associations in UK Biobank

Genome-wide association studies have revealed many loci contributing to the variation of complex traits, yet the majority of loci that contribute to the heritability of complex traits remain elusive. Large study populations with sufficient statistical power are required to detect the small effect sizes of the yet unidentified genetic variants. However, the analysis of huge cohorts, like UK Biobank, is complicated by incidental structure present when collecting such large cohorts. For instance, UK Biobank comprises 107,162 third degree or closer related participants. Traditionally, GWAS have removed related individuals because they comprised an insignificant proportion of the overall sample size, however, removing related individuals in UK Biobank would entail a substantial loss of power. Furthermore, modelling such structure using linear mixed models is computationally expensive, which requires a computational infrastructure that may not be accessible to all researchers. Here we present an atlas of genetic associations for 118 non-binary and 599 binary traits of 408,455 related and unrelated UK Biobank participants of White-British descent. Results are compiled in a publicly accessible database that allows querying genome-wide association summary results for 623,944 genotyped and HapMap2 imputed SNPs, as well downloading whole GWAS summary statistics for over 30 million imputed SNPs from the Haplotype Reference Consortium panel. Our atlas of associations (GeneATLAS, http://geneatlas.roslin.ed.ac.uk) will help researchers to query UK Biobank results in an easy way without the need to incur in high computational costs.

genomics