Ontology type: schema:ScholarlyArticle Open Access: True
2017-12
AUTHORSCatherine Igartua, Sahar V. Mozaffari, Dan L. Nicolae, Carole Ober
ABSTRACTFounder populations are ideally suited for studies on the clinical effects of alleles that are rare in general populations but occur at higher frequencies in these isolated populations. Whole genome sequencing in 98 Hutterites, a founder population of European descent, and subsequent imputation revealed 660,238 single nucleotide polymorphisms that are rare (<1%) or absent in European populations, but occur at frequencies >1% in the Hutterites. We examined the effects of these rare in European variants on plasma lipid levels in 828 Hutterites and applied a Bayesian hierarchical framework to prioritize potentially causal variants based on functional annotations. We identified two novel non-coding rare variants associated with LDL cholesterol (rs17242388 in LDLR) and HDL cholesterol (rs189679427 between GOT2 and APOOP5), and replicated previous associations of a splice variant in APOC3 (rs138326449) with triglycerides and HDL-C. All three variants are at well-replicated loci in GWAS but are independent from and have larger effect sizes than the known common variation in these regions. Candidate eQTL analyses in in LCLs in the Hutterites suggest that these rare non-coding variants are likely to mediate their effects on lipid traits by regulating gene expression. More... »
PAGES16415
http://scigraph.springernature.com/pub.10.1038/s41598-017-16550-8
DOIhttp://dx.doi.org/10.1038/s41598-017-16550-8
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/29180722
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