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GWAS Study

Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

Pazoki R, Vujkovic M, Elliott J et al.

33972514 PubMed ID
GWAS Study Type
752839 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

PR
Pazoki R
VM
Vujkovic M
EJ
Elliott J
EE
Evangelou E
GD
Gill D
GM
Ghanbari M
VD
van der Most PJ
PR
Pinto RC
WM
Wielscher M
FM
Farlik M
ZV
Zuber V
DK
de Knegt RJ
SH
Snieder H
UA
Uitterlinden AG
LJ
Lynch JA
JX
Jiang X
SS
Said S
KD
Kaplan DE
LK
Lee KM
SM
Serper M
CR
Carr RM
TP
Tsao PS
AS
Atkinson SR
DA
Dehghan A
TI
Tzoulaki I
IM
Ikram MA
HK
Herzig KH
JM
Järvelin MR
AB
Alizadeh BZ
OC
O'Donnell CJ
SD
Saleheen D
VB
Voight BF
CK
Chang KM
TM
Thursz MR
EP
Elliott P
Chapter II

Abstract

Summary of the research findings

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

437,267 European ancestry individuals

Chapter III

Study Statistics

Key metrics and study information

752839
Total Participants
GWAS
Study Type
Yes
Replicated
315,572 European ancestry individuals
Replication Participants
European
Ancestry
Netherlands, U.S., U.K.
Recruitment Country
Chapter IV

AI-Generated Summary

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