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Background. Behavioral genetic fndings suggest that complex traits, such as mathemat-ical ability, general cognitive ability (intelligence; g), and spatial ability, are infuenced by many common genetic variants of very small efects that operate across the ability \ud continuum. Common genetic variants may also be responsible for cognitive defcits as-sociated with rare genetic syndromes, in which whole genomic regions may be afected. To date, relatively few common genetic variants involved in cognitive traits have been \ud identifed, and these only explain a small proportion of variance in these traits.\ud \ud Objective. Te aim of the study was to fnd associations between mathematics-re-lated traits and single-nucleotide polymorphisms (SNPs) within chromosomal regions involved in Williams and Prader-Willi disorders. Both disorders are characterized by \ud patterns of weaknesses and strengths in cognitive abilities. Two types of analyses were performed (SNP-based and gene-based), using genotypic and phenotypic data available for 3000 participants from the UK. \ud \ud Results. SNP-based tests indicated that none of the SNPs passed the demanding multiple testing correction level for any of the phenotypes. Gene-based analysis sug-gested that 2 pseudogenes (i.e., GOLGA8I and WHAMMP3) were signifcantly asso-ciated with intelligence, and 1 gene (i.e., TUBGCP5) was signifcantly associated with mathematics at 16 years of age. \ud \ud Conclusion. Te results are consistent with other fndings demonstrating that cog-nitive traits are infuenced by many common genetic variants with very small efects. The results also suggest that a small number of these variants may be located in the chromo-somal regions afected in Prader-Willi and Williams syndrome regions.

It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024-rs2061174-rs324650) has been significantly associated with MDD in a previous study. We report the first study investigating this gene in a large, adequately powered, clinical depression case-control sample (n = 1420 cases, 1624 controls). Our data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. It is possible our failure to replicate may be a consequence of differences in definition of the MDD phenotype and/or ethnic differences.

The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case–control association samples for 18 common diseases. Here we present the results of a follow-up case–control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A). Within the current study, we attempted to follow-up these findings in a sample from the UK, the Depression Case Control (DeCC) sample consisting of 1,196 cases and 842 screened controls, phenotyped using exactly the same methods as the MP-GSK sample. Performing Cochran–Mantel–Haenzel statistics to test for genotypic and/or allelic differences between the DeCC and MP-GSK samples, we found no significant differences, thus being able to combine the two samples for association testing. In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis.

The gene known as Disrupted-in-Schizophrenia-1, DISC1, was originally discovered in a large family, in which it also co-segregated with bipolar affective disorder (BD) and with major depressive disorder (MDD). The TSNAX (Translin-associated factor X) gene, located immediately upstream of DISC1, has also been suggested as a candidate gene in relation to psychiatric illness, as one transcript resulting from intergenic splicing encodes a novel TSNAX–DISC1 fusion protein. We explored the TSNAX–DISC1 gene region for an association with BD and MDD in a sample of 1984 patients (1469 MDD, 515 BD) and 1376 ethnically matched controls. Eight single nucleotide polymorphisms (SNPs) within the TSNAX–DISC1 region (rs766288, rs3738401, rs2492367, rs6675281, rs12133766, rs1000731, rs7546310 and rs821597) were investigated using the SNPlex Genotyping System. We found a significant allelic and genotypic association of the TSNAX–DISC1 gene region with BD, whereas a haplotypic association was found for both BD and MDD. Therefore, our results suggest an association between the TSNAX–DISC1 region and both forms of affective disorders, and support the hypothesis that a portion of the genotypic overlap between schizophrenia and affective disorders is attributable to this gene.

The focus on gender-specific genes associated with female suicide is justified by the possible dimorphic nature of the serotonergic system and by the greater number of suicide attempts in females. We performed analysis of the promoter (5-HTTLPR) and intron 2 (STin2 VNTR) polymorphisms and haplotypes of the serotonin transporter gene in Russian suicide attempters, separately in men and women. Our findings indicate the contribution of the SLC6A4 gene to susceptibility for suicidal behavior in women, but not in men. The L/L genotype (p = 0.013, OR = 2.09) and L10 haplotype (p = 0.04, OR = 1.77) were associated with suicide in Russian women only. Further investigations of this gene in different phenotypic groups are necessary.