Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI

Article (PDF Available)inDiabetes 59(3):751-5 · November 2009with22 Reads
DOI: 10.2337/db09-0972 · Source: PubMed
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. 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). 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. 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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    • "Interestingly, many of the loci that have been shown to be associated with T2D have been implicated in birth weight determination [43–47]. Similarly, it has also been shown that the T2D-associated locus in HHEX is associated with increased childhood body mass index (BMI) [48]. This means that the influence of these T2D risk loci may exert their effects early on in life. "
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    • "Several studies have also investigated the relationship between HHEX polymorphisms and other metabolic diseases. Zhao et al.[24] found that the type 2 diabetes risk-associated G allele of rs7923837 was associated with higher pediatric BMI in European American children. Cruz et al.[25] analyzed the association between the HHEX rs5015480 and risk of metabolic syndrome (MS) in a case-control study from Mexico city and found that rs5015480 was significantly associated with MS. "
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