Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, D-45147 Essen, Germany.
Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):295-305. doi: 10.1002/ajmg.b.32144. Epub 2013 Mar 26.
Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P = 3.4 × 10(-4) ; Pcorr = 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 × 10(-4) ; Pcorr = 0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity.
患有注意力缺陷多动障碍（ADHD）的儿童比没有 ADHD 的儿童肥胖率更高。肥胖风险等位基因可能与 ADHD 相关的风险等位基因重叠。我们研究了增加体重指数（BMI）的风险等位基因是否与 ADHD 及相关的定量特征（注意力不集中和多动/冲动）相关。我们基于 495 名患者和 1300 名基于人群的对照，对 ADHD 的全基因组关联研究（GWAS）中的 32 个肥胖风险单核苷酸多态性（SNP）进行了筛查，并对包含 2064 个三体型、896 个独立病例和 2455 个对照的 ADHD 荟萃分析中的 SNPs 进行了基于生物信息学的分析。在德国样本中，NUDT3 基因中的 rs206936（nudix；核苷酸二磷酸连接部分 X 型基序 3）与 ADHD 风险相关（OR：1.39；P=3.4×10(-4)；Pcorr=0.01）。在荟萃分析数据中，我们发现 GPRC5B 基因内含子区域的 rs6497416（G 蛋白偶联受体，家族 C，组 5，成员 B；P=7.2×10(-4)；Pcorr=0.02）是 ADHD 的风险等位基因。GPRC5B 属于代谢型谷氨酸受体家族，该家族与 ADHD 的病因有关。在德国样本中，rs206936（NUDT3）和 GNPDA2 基因（葡萄糖胺-6-磷酸脱氨酶 2）中的 rs10938397 与注意力不集中有关，而 MAP2K5 基因（丝裂原活化蛋白激酶 5）和 CADM2 基因（细胞黏附分子 2）中的标记物与多动/冲动有关。在荟萃分析数据中，MAP2K5 与注意力不集中有关，GPRC5B 与多动/冲动和注意力不集中有关，CADM2 与多动/冲动有关。我们的研究结果证明，有必要进一步研究 ADHD 和肥胖的共同遗传背景。
