Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ligthart:2016:10.1186/s12864-016-2712-4,
author = {Ligthart, S and Vaez, A and Hsu, YH and Stolk, R and Uitterlinden, AG and Hofman, A and Alizadeh, BZ and Franco, OH and Dehghan, A},
doi = {10.1186/s12864-016-2712-4},
journal = {BMC Medical Genomics},
title = {Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation},
url = {http://dx.doi.org/10.1186/s12864-016-2712-4},
volume = {17},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: Genome-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. Results: In 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 S NPs for CRP in or near CTSB/FDFT1 (rs10435719, P replication : 2.6 × 10 -5 ), STAG1/PCCB (rs7621025, P replication : 1.4 × 10 -3 ) and FTO (rs1558902, P replication : 2.7 × 10 -5 ). 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. Conclusions: Our 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.
AU - Ligthart,S
AU - Vaez,A
AU - Hsu,YH
AU - Stolk,R
AU - Uitterlinden,AG
AU - Hofman,A
AU - Alizadeh,BZ
AU - Franco,OH
AU - Dehghan,A
DO - 10.1186/s12864-016-2712-4
PY - 2016///
SN - 1755-8794
TI - Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation
T2 - BMC Medical Genomics
UR - http://dx.doi.org/10.1186/s12864-016-2712-4
UR - http://hdl.handle.net/10044/1/52884
VL - 17
ER -