Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Diabetes. 2010 Mar;59(3):751-5. doi: 10.2337/db09-0972. Epub 2009 Nov 23.
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.
多项研究发现，生命早期的 BMI 会影响日后发生 2 型糖尿病的风险。我们的目标是研究通过全基因组关联研究（GWAS）发现的任何 2 型糖尿病变异是否会影响儿童时期的 BMI。
利用我们队列中正在进行的儿科 BMI 全基因组关联研究的数据，我们调查了儿科 BMI 与通过 GWAS 发现的 18 个 2 型糖尿病位点的 20 个单核苷酸多态性之间的关联，这些位点包括 ADAMTS9、CDC123-CAMK1D、CDKAL1、CDKN2A/B、EXT2、FTO、HHEX-IDE、IGF2BP2、11p12 基因内区域、JAZF1、KCNQ1、LOC387761、MTNR1B、NOTCH2、SLC30A8、TCF7L2、THADA 和 TSPAN8-LGR5。我们将队列随机分成两半，以便有一个发现队列（n = 3592）和一个复制队列（n = 3592）。
我们的数据显示，HHEX-IDE 位点的主要 2 型糖尿病风险 G 等位基因 rs7923837 与发现（P = 0.0013，经 20 次检验校正后仍存在）和复制（P = 0.023）两组儿童 BMI 均较高相关（联合 P = 1.01 x 10(-4)）。除了已确立的 FTO 外，尚未发现与迄今为止通过 GWAS 发现的任何其他已知 2 型糖尿病位点有关联。
我们的数据显示，与先前研究中 2 型糖尿病相关的相同遗传 HHEX-IDE 变异也会影响儿童 BMI。
