BioProject

Genetic studies in isolated populations have elucidated many high frequency, large effect protein-coding variants. More...

Genetic studies in isolated populations have elucidated many high frequency, large effect protein-coding variants. To identify the contribution of non-coding variation on population- and individual-specific genetic risk factors we have combined whole genome and transcriptome data from 624 Sardinians to identify common and rare non-coding variants influencing expression and splicing. We identified 21,183 independent expression quantitative trait loci (eQTLs) and 6,768 independent splicing quantitative trait loci (sQTLs) including 655 novel QTLs with population-specific trait associations. We further identified high frequency QTLs and patterns of selection at genes involved in malarial resistance and multiple sclerosis, reflecting the long-term epidemiological history of the island. Using family relationships, we identified 809 segregating expression outliers (median z-score of 2.97) averaging 13.3 genes per individual. We observe that outliers are enriched for rare variants providing new means to study large effect variants of relevance to multiple traits. Our results provide new insight into the effects of non-coding variants and their relationship to population history and individual genetic risk. Less...