Examination of All Type 2 Diabetes GWAS Loci Reveals HHEX-IDE As a Locus Influencing Pediatric BMI

Overview

Journal Diabetes

Specialty Endocrinology

Date 2009 Nov 26

PMID 19933996

Citations 30

Authors

Jianhua Zhao

Jonathan P Bradfield

Haitao Zhang

Kiran Annaiah

Kai Wang

Cecilia E Kim

Joseph T Glessner

Edward C Frackelton

F George Otieno

James Doran

Kelly A Thomas

Maria Garris

Cuiping Hou

Rosetta M Chiavacci

Mingyao Li

Robert I Berkowitz

Hakon Hakonarson

Struan F A Grant

Affiliations

Soon will be listed here.

Abstract

Objective: A number of studies have found that BMI in early life influences the risk of developing type 2 diabetes later in life. Our goal was to investigate if any type 2 diabetes variants uncovered through genome-wide association studies (GWAS) impact BMI in childhood.

Research Design And Methods: Using data from an ongoing GWAS of pediatric BMI in our cohort, we investigated the association of pediatric BMI with 20 single nucleotide polymorphisms at 18 type 2 diabetes loci uncovered through GWAS, consisting of ADAMTS9, CDC123-CAMK1D, CDKAL1, CDKN2A/B, EXT2, FTO, HHEX-IDE, IGF2BP2, the intragenic region on 11p12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and TSPAN8-LGR5. We randomly partitioned our cohort exactly in half in order to have a discovery cohort (n = 3,592) and a replication cohort (n = 3,592).

Results: Our data show that the major type 2 diabetes risk-conferring G allele of rs7923837 at the HHEX-IDE locus was associated with higher pediatric BMI in both the discovery (P = 0.0013 and survived correction for 20 tests) and replication (P = 0.023) sets (combined P = 1.01 x 10(-4)). Association was not detected with any other known type 2 diabetes loci uncovered to date through GWAS except for the well-established FTO.

Conclusions: Our data show that the same genetic HHEX-IDE variant, which is associated with type 2 diabetes from previous studies, also influences pediatric BMI.

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