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Analysis with the exome array identifies multiple new independent variants in lipid loci.

Hum. Mol. Genet. 25, 4094-4106 (2016)
Publishers Version Postprint DOI PMC
Open Access Green
as soon as is submitted to ZB.
It has been hypothesised that low frequency (1-5% MAF) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27,312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000 fold more significant than the previous sentinel variant and not in close LD (6 had MAF < 5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1-5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5-2.5 fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Coronary-artery-disease; Low-frequency; Ldl-cholesterol; Blood-lipids; Rare; Heritability; Metaanalysis; Transporter; Traits
Reviewing status