Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects Ϸ1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study metaanalysis was 2.4 ؋ 10 ؊6 . We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P Ϸ 10 ؊7 : 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (MCTP1). The most strongly associated nonsynonymous SNP rs1042779 (OR ‫؍‬ 1.19, P ‫؍‬ 1.8 ؋ 10 ؊7 ) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3, NEK4, and ITIH3. Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR ‫؍‬ 1.37, P ‫؍‬ 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.genetics ͉ genome-wide association study B ipolar disorder (BP) is characterized by dramatic mood changes, with individuals experiencing alternating episodes of depression and mania interspersed with periods of normal function. BP is chronic, severely disabling, and life-threatening, with increased risk of suicide and estimated lifetime prevalence of Ϸ1% (1).BP has a substantial genetic component. Monozygotic twin concordance rate estimates range from 45 to 70% and sibling recurrence risk estimates from 5 to 10 (2). Nonetheless, the underlying genetic and neurobiological triggers of BP remain elusive. Numerous linkage and candidate gene studies have sought to identify BP linked regions and associated genes, but no loci have been convincingly identified. Several groups have recently reported results of BP genome-wide association studies (GWAS), using pooled (3) or individually genotyped (4-6) samples; these studies identified SNPs in CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel), ANK3 (ankyrin 3), and DGKH (diacylglycerol kinase, eta) as potentially associated with BP.To test for SNP-BP association in additional well-characterized samples, we analyzed data for Ͼ2.3 million genotyped and imputed SNPs on Ͼ3,700 individuals in 2 sample sets: (i) 1,177 bipolar I ...

Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10−6) and GPC6 showed suggestive evidence for interaction with age (p≈10−7). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

In this paper an automatic deception detection system, which analyses participant deception risk scores from non-verbal behaviour captured during an interview conducted by an Avatar, is demonstrated. The system is built on a configuration of artificial neural networks, which are used to detect facial objects and extract non-verbal behaviour in the form of micro gestures over short periods of time. A set of empirical experiments was conducted based a typical airport security scenario of packing a suitcase. Data was collected through 30 participants participating in either a truthful or deceptive scenarios being interviewed by a machine based border guard Avatar. Promising results were achieved using raw unprocessed data on un-optimized classifier neural networks. These indicate that a machine based interviewing technique can elicit non-verbal interviewee behavior, which allows an automatic system to detect deception.