Loci affecting gamma-glutamyl transferase in adults and adolescents show age × SNP interaction and cardiometabolic disease associations.
Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 × 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 × 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 × 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 × 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.
Queensland Institute of Medical Research, Brisbane, Australia.
Rita P
RP
Middelberg
Beben
B
Benyamin
Marleen H M
MH
de Moor
Nicole M
NM
Warrington
Scott
S
Gordon
Anjali K
AK
Henders
Sarah E
SE
Medland
Dale R
DR
Nyholt
Eco J C
EJ
de Geus
Jouke J
JJ
Hottenga
Gonneke
G
Willemsen
Lawrence J
LJ
Beilin
Trevor A
TA
Mori
Margaret J
MJ
Wright
Andrew C
AC
Heath
Pamela A F
PA
Madden
Dorret I
DI
Boomsma
Craig E
CE
Pennell
Grant W
GW
Montgomery
Nicholas G
NG
Martin
John B
JB
Whitfield
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D018740:Genetic Heterogeneity; D055106:Genome-Wide Association Study; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D008659:Metabolic Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D005723:gamma-Glutamyltransferase / Q000235:genetics*
D005723:gamma-Glutamyltransferase