rs140700

Family-based association study of 290 Caucasian families investigating SLC6A4 and ITGB3 genes in autism, stratified by family history. While individual SNPs showed no significant associations after multiple testing correction, stratification by family history revealed nominally significant associations at rs2066713 (SLC6A4) in both positive and negative family history groups, and rs3809865 (ITGB3) in positive family history families. Gene-gene interaction analysis confirmed a significant interaction between rs2066713 (SLC6A4) and rs5918 (ITGB3, Leu33Pro) (p=0.014, survived multiple testing correction), suggesting family history is an important index of genetic heterogeneity in autism susceptibility.

This association study examined whether variants in the serotonin transporter gene (SLC6A4) are associated with Neuroticism-related personality traits in two large cohorts: the SardiNIA population (N=3,913 for 5-HTTLPR; N=3,972 for SNPs) and the Baltimore Longitudinal Study of Aging (N=548 for 5-HTTLPR; N=1,182 for SNPs). Using the NEO-PI-R personality assessment, the study found no significant association between the 5-HTTLPR polymorphism and Neuroticism or its facets in the SardiNIA sample, and only inconsistent weak associations with the opposite direction in the BLSA sample. Examination of 8-9 additional SNPs in the SLC6A4 gene region (including rs8071667 and rs140700) showed no significant associations after multiple testing correction, contradicting prior meta-analytic findings and providing strong evidence against a main effect of common SLC6A4 variants on Neuroticism traits.

This family-based association study investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for sexually dimorphic genetic effects in 474 ADHD-affected offspring. The Met allele of COMT Val158Met showed stronger association in males (OR=1.42, p=0.003) but not females (p=0.936), and when combined with prior data showed significant gender effects (p=0.007). SLC6A2 and MAOA also showed sex-stratified associations, supporting the hypothesis that ADHD risk genes have sexually dimorphic effects.

Haplotype-tagging SNP analysis in 364 individuals from 152 ADHD families identified significant associations between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596) and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are valid ADHD endophenotypes linked to dopaminergic and noradrenergic pathways.