Adhesion G protein-coupled receptor L3 gene variants: Statistically significant association observed in the male Indo-caucasoid Attention deficit hyperactivity disorder probands

Primary symptoms of Attention Deficit Hyperactivity Disorder (ADHD) are age inappropriate inattention, hyperactivity and impulsivity. Caucasoid individuals showed increased susceptibility to ADHD and disruptive behaviour in presence of Adhesion G-protein-coupled receptor L3 (ADGRL3) gene variants. We investigated ADGRL3 rs1868790, rs6551665, rs2345039 in Indo-Caucasoid families with ADHD probands (N = 249) and controls (N = 350). Behavioural traits, executive function, and IQ of probands were measured through Conner's Parent Rating Scale-Revised, Parental Account of Children's Symptoms, Barkley Deficit in Executive Functioning-Child & Adolescent Scale, and Wechsler Intelligence Scale for Children-III respectively. After obtaining informed written consent, peripheral blood was collected for genomic DNA isolation and target sites were analyzed by PCR based methods or TaqMan assay. Case-control analysis showed higher frequency of rs2345039 'C' allele, 'CC' genotype and A-A-C haplotype in the ADHD probands, principally due to higher occurrence of the 'C' allele and A-A-C haplotype in the male probands (P < 0.05). Mother of the probands also showed higher occurrence of the 'C' allele and "CC" genotype (P < 0.01). Executive function was better in presence of rs2345039 "GG" (P = 0.04) while IQ score was higher in presence of rs6551665 "AA" (P = 0.06). Linkage disequilibrium between rs6551665 and rs2345039 was stronger in the ADHD cases, chiefly in the male probands. Multifactor dimensionality reduction analysis showed strong interaction between rs6551665 and rs2345039 in the male probands while in the female probands rs1868790 and rs6551665 revealed non-linear interaction. Based on these observations, we infer that ADGRL3 may have a role in the aetiology of ADHD in this population warranting further in depth investigation.