ADGRL3 polymorphisms linked to ADHD susceptibility in children

An association exists between the gene encoding adhesion G protein-coupled receptor L3 (ADGRL3) and childhood attention-deficit/hyperactivity disorder (ADHD), which is consistent with the gene’s role in early neurodevelopment, reports a study.

A systematic review and a comprehensive meta-analysis were conducted to examine the associations between the most studies ADGRL3 polymorphisms (rs6551665, rs1947274, rs1947275, and rs2345039) and both childhood and adulthood ADHD.

Eight association studies (seven published and one unpublished) were included in the meta-analysis. Genome-wide association study (GWAS) data were also incorporated for ADGRL3. The investigators avoided overlapping samples by starting with summary statistics from GWAS samples and then adding data from gene association studies.

ADGRL3 variants appeared to have an effect on ADHD susceptibility in children (n=8,724 participants; n=14,644 controls; n=1,893 families): rs6551665 A allele (Z score, −2.701; p=0.0069); rs1947274 A allele (Z score, −2.033; p=0.0421); rs1947275 T allele (Z score, 2.339; p=0.0978); and rs2345039 C allele (Z score, 3.806; p=0.0026).

Analyses revealed heterogeneity for three single nucleotide polymorphisms (SNPs), namely rs6551665, rs1947274, and rs2345039.

Results were not significant in adults (n=6,532 individuals; n=15,874 controls): rs6551665 A allele (Z score, 2.005; p=0.0450); rs1947274 A allele (Z score, 2.179; p=0.0293); rs1947275 T allele (Z score, −0.822; p=0.4109); and rs2345039 C allele (Z score, −1.544; p=0.1226). Heterogeneity was found for only one SNP, namely rs6551665.

Moreover, funnel plots did not show any publication bias.

“The gene encoding ADGRL3, also referred to as latrophilin 3 or LPHN3, has been associated with ADHD susceptibility in independent ADHD [individuals],” the investigators noted.