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Meta-analysis and systematic review of ADGRL3 (LPHN3) polymorphisms in ADHD susceptibility

Version 2 2024-06-13, 07:15
Version 1 2020-03-04, 14:40
journal contribution
posted on 2024-06-13, 07:15 authored by EM Bruxel, CR Moreira-Maia, GC Akutagava-Martins, TP Quinn, M Klein, B Franke, M Ribasés, P Rovira, C Sánchez-Mora, DB Kappel, NR Mota, EH Grevet, CHD Bau, M Arcos-Burgos, LA Rohde, MH Hutz
The gene encoding adhesion G protein-coupled receptor L3 (ADGRL3, also referred to as latrophilin 3 or LPHN3) has been associated with ADHD susceptibility in independent ADHD samples. We conducted a systematic review and a comprehensive meta-analysis to summarize the associations between the most studied ADGRL3 polymorphisms (rs6551665, rs1947274, rs1947275, and rs2345039) and both childhood and adulthood ADHD. Eight association studies (seven published and one unpublished) fulfilled criteria for inclusion in our meta-analysis. We also incorporated GWAS data for ADGRL3. In order to avoid overlapping samples, we started with summary statistics from GWAS samples and then added data from gene association studies. The results of our meta-analysis suggest an effect of ADGRL3 variants on ADHD susceptibility in children (n = 8724/14,644 cases/controls and 1893 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). Heterogeneity was found in analyses for three SNPs (rs6551665, rs1947274, and rs2345039). In adults, results were not significant (n = 6532 cases/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 just for rs6551665. In addition, funnel plots did not suggest publication biases. Consistent with ADGRL3’s role in early neurodevelopment, our findings suggest that the gene is predominantly associated with childhood ADHD.

History

Journal

Molecular Psychiatry

Volume

26

Pagination

2277-2285

Location

England

ISSN

1359-4184

eISSN

1476-5578

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

6

Publisher

SPRINGERNATURE