Analysis with the exome array identifies multiple new independent variants in lipid loci
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
It has been hypothesized that low frequency (1-5% minor allele frequency (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 (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 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.
Originalsprog | Engelsk |
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Tidsskrift | Human Molecular Genetics |
Vol/bind | 25 |
Udgave nummer | 18 |
Sider (fra-til) | 4094-4106 |
Antal sider | 13 |
ISSN | 0964-6906 |
DOI | |
Status | Udgivet - 15 sep. 2016 |
Eksternt udgivet | Ja |
ID: 242837559