Analysis with the exome array identifies multiple new independent variants in lipid loci
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Human Molecular Genetics |
Volume | 25 |
Issue number | 18 |
Pages (from-to) | 4094-4106 |
Number of pages | 13 |
ISSN | 0964-6906 |
DOIs | |
Publication status | Published - 15 Sep 2016 |
Externally published | Yes |
Bibliographical note
© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
- Adolescent, Adult, Aged, Child, Cholesterol, HDL/blood, Cholesterol, LDL/blood, European Continental Ancestry Group, Exome/genetics, Gene Frequency, Genome-Wide Association Study, Humans, Lipid Metabolism/genetics, Lipids/blood, Middle Aged, Polymorphism, Single Nucleotide, Triglycerides/blood
Research areas
ID: 242837559