Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammationReport as inadecuate

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BMC Genomics

, 17:443

Human and rodent genomics


BackgroundGenome-wide association studies GWAS have identified multiple genetic loci for C-reactive protein CRP and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism.

ResultsIn a bivariate GWAS, we combined summary statistics of published GWAS on CRP n = 66,185 and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol n = 100,184, using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB-FDFT1 rs10435719, Preplication: 2.6 × 10, STAG1-PCCB rs7621025, Preplication: 1.4 × 10 and FTO rs1558902, Preplication: 2.7 × 10. Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.

ConclusionsOur large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.

KeywordsC-reactive protein Inflammation Lipids Genome-wide association study Genetic pleiotropy AbbreviationsCRPC-reactive protein

GWASgenome-wide association study

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-2712-4 contains supplementary material, which is available to authorized users.

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Author: Symen Ligthart - Ahmad Vaez - Yi-Hsiang Hsu - Inflammation Working Group of the CHARGE Consortium - PMI-WG-XCP - LifeLines Coho


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