1Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Oct 153B: 1276-82
TitleAssociation analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample.
AbstractA recent genome-wide association study (GWAS) found significant association between the PALB2 SNP rs420259 and bipolar disorder (BD). The intracellular functions of the expressed proteins from the breast cancer risk genes PALB2 and BRCA2 are closely related. Therefore, we investigated the relation between genetic variants in PALB2 and BRCA2 and BD. Due to increasing evidence of genetic overlap between BD and schizophrenia (SCZ), we also investigated association with SCZ. In a Scandinavian case-control sample (n?=?686/2,538) we found the BRCA2 SNP rs9567552 to be significantly associated with BD (Nominal P?=?0.00043). Additionally, we replicated the association between PALB2 SNP rs420259 and BD (Nominal P?=?0.025). We then combined our sample with another Nordic case-control sample (n?=?435/11,491) from Iceland, and added results from the Wellcome Trust Case Control Consortium (WTCCC) (n?=?1,868/2,938) and the STEP-UCL/ED-DUB-STEP2 study (n?=?2,558/3,274) in a meta-analysis which revealed a P-value of 1.2??10(-5) for association between PALB2 SNP rs420259 and BD (n?=?5,547/20,241). Neither the PALB2 SNP rs420259 nor the BRCA2 SNP rs9567552 were nominally significantly associated with the SCZ phenotype in our Scandinavian sample (n?=?781/2,839). Our findings support PALB2 and BRCA2 as risk genes specifically for BD, and suggest that altered DNA repair related to neurogenesis may be involved in BD pathophysiology. 2010 Wiley-Liss, Inc.
SCZ Keywordsschizophrenia
2PLoS ONE 2014 -1 9: e112559
TitleGenome-wide and gene-based association studies of anxiety disorders in European and African American samples.
AbstractAnxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of schizophrenia (MGS) project (2,540 European American and 849 African American subjects) genotyped on the Affymetrix GeneChip 6.0 array. We applied two phenotypic approaches: (1) categorical case-control comparisons (CC) based upon psychiatric diagnoses, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. Linear and logistic models were used to analyse the association with ADs using FS and CC traits, respectively. At the single locus level, no genome-wide significant association was found. A trans-population gene-based meta-analysis across both ethnic subsamples using FS identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12) with genome-wide significance (false discovery rate (FDR] <5%). At the pathway level, several terms such as transcription regulation, cytokine binding, and developmental process were significantly enriched in ADs (FDR <5%). Our approaches studying ADs as quantitative traits and utilizing the full GWAS data may be useful in identifying susceptibility genes and pathways for ADs.
SCZ Keywordsschizophrenia