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{Speliotes:2011:10.1371/journal.pgen.1001324,
author = {Speliotes, EK and Yerges-Armstrong, LM and Wu, J and Hernaez, R and Kim, LJ and Palmer, CD and Gudnason, V and Eiriksdottir, G and Garcia, ME and Launer, LJ and Nalls, MA and Clark, JM and Mitchell, BD and Shuldiner, AR and Butler, JL and Tomas, M and Hoffmann, U and Hwang, SJ and Massaro, JM and O'Donnell, CJ and Sahani, DV and Salomaa, V and Schadt, EE and Schwartz, SM and Siscovick, DS and Voight, BF and Carr, JJ and Feitosa, MF and Harris, TB and Fox, CS and Smith, AV and Kao, WH and Hirschhorn, JN and Borecki, IB},
doi = {10.1371/journal.pgen.1001324},
journal = {PLOS Genetics},
title = {Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits},
url = {http://dx.doi.org/10.1371/journal.pgen.1001324},
volume = {7},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable ( approximately 26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and approximately 2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5x10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
AU - Speliotes,EK
AU - Yerges-Armstrong,LM
AU - Wu,J
AU - Hernaez,R
AU - Kim,LJ
AU - Palmer,CD
AU - Gudnason,V
AU - Eiriksdottir,G
AU - Garcia,ME
AU - Launer,LJ
AU - Nalls,MA
AU - Clark,JM
AU - Mitchell,BD
AU - Shuldiner,AR
AU - Butler,JL
AU - Tomas,M
AU - Hoffmann,U
AU - Hwang,SJ
AU - Massaro,JM
AU - O'Donnell,CJ
AU - Sahani,DV
AU - Salomaa,V
AU - Schadt,EE
AU - Schwartz,SM
AU - Siscovick,DS
AU - Voight,BF
AU - Carr,JJ
AU - Feitosa,MF
AU - Harris,TB
AU - Fox,CS
AU - Smith,AV
AU - Kao,WH
AU - Hirschhorn,JN
AU - Borecki,IB
DO - 10.1371/journal.pgen.1001324
PY - 2011///
SN - 1553-7390
TI - Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits
T2 - PLOS Genetics
UR - http://dx.doi.org/10.1371/journal.pgen.1001324
UR - http://hdl.handle.net/10044/1/28747
VL - 7
ER -