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 Eight association studies (seven published and one unpublished) fulfilled criteria for inclusion in our meta-analysis.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.

中文翻译：

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ADGRL3 (LPHN3) 多态性在 ADHD 易感性中的 Meta 分析和系统评价。

编码粘附 G 蛋白偶联受体 L3（ADGRL3，也称为 latrophilin 3 或 LPHN3）的基因与独立 ADHD 样本中的 ADHD 易感性有关。我们进行了系统回顾和综合荟萃分析，总结了研究最多的 ADGRL3 多态性（rs6551665、rs1947274、rs1947275 和 rs2345039）与儿童和成人 ADHD 之间的关联。八项关联研究（七项已发表，一项未发表）符合纳入我们荟萃分析的标准。我们还整合了 ADGRL3 的 GWAS 数据。为了避免样本重叠，我们从 GWAS 样本的汇总统计开始，然后添加来自基因关联研究的数据。我们的荟萃分析结果表明 ADGRL3 变体对儿童 ADHD 易感性的影响（n = 8724/14，644 例/对照和 1893 个家庭）：rs6551665 A 等位基因（Z 得分 = -2.701；p = 0.0069）；rs1947274 A 等位基因（Z 得分 = -2.033；p = 0.0421）；rs1947275 T 等位基因（Z 得分 = 2.339；p = 0.0978）；和 rs2345039 C 等位基因（Z 分数 = 3.806；p = 0.0026）。在对三个 SNP（rs6551665、rs1947274 和 rs2345039）的分析中发现了异质性。在成人中，结果不显着（n = 6532 例/15,874 对照）：rs6551665 A 等位基因（Z 评分 = 2.005；p = 0.0450）；rs1947274 A 等位基因（Z 得分 = 2.179；p = 0.0293）；rs1947275 T 等位基因（Z 分数 = -0.822；p = 0.4109）；和 rs2345039 C 等位基因（Z 得分 = -1.544；p = 0.1226）。仅针对 rs6551665 发现了异质性。此外，漏斗图并未显示出发表偏倚。与 ADGRL3 在早期神经发育中的作用一致，