Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women.

ABSTRACT: Sex differences in schizophrenia are well known, but their genetic basis has not been identified. We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling. We found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin (RELN) gene (p = 2.9 x 10(-5) in women), with a significant gene-sex effect (p = 1.8 x 10(-4)). We studied rs7341475 in four additional populations, totaling 2,274 cases and 4,401 controls. A significant effect was observed only in women, replicating the initial result (p = 2.1 x 10(-3) in women; p = 4.2 x 10(-3) for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 x 10(-7); p = 1.6 x 10(-5) for gene-sex interaction). The female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.

SUBMITTER: Shifman S

PROVIDER: S-EPMC2242812 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women.

Project description:A single nucleotide polymorphism (rs7341475) in RELN has recently been shown to be associated with schizophrenia (SZ) in an Ashkenazi Jewish (AJ) case--control study specifically in women by Shifman et al. We have replicated this association in women in another large independent Ashkenazi Jewish collection (721 cases, 259 female; 1455 controls, 834 female) and confirmed that it applies to both SZ and schizoaffective disorder. Furthermore, we explore the effects of this polymorphism through quantitative trait loci analysis of nine SZ related factors providing information on sex-specific genotype--phenotype correlations.

| S-EPMC2901865 | biostudies-literature

Genome-wide association study identifies a common variant associated with risk of endometrial cancer.

Project description:Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.

| S-EPMC3770523 | biostudies-literature

Genome-wide association study identifies five new schizophrenia loci.

Project description:We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

| S-EPMC3303194 | biostudies-literature

Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk.

Project description:We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).

| S-EPMC3722904 | biostudies-literature

Genome-wide association identifies diverse causes of common variable immunodeficiency.

Project description:BackgroundCommon variable immunodeficiency (CVID) is a heterogeneous immune defect characterized by hypogammaglobulinemia, failure of specific antibody production, susceptibility to infections, and an array of comorbidities.ObjectiveTo address the underlying immunopathogenesis of CVID and comorbidities, we conducted the first genome-wide association and gene copy number variation (CNV) study in patients with CVID.MethodsThree hundred sixty-three patients with CVID from 4 study sites were genotyped with 610,000 single nucleotide polymorphisms (SNPs). Patients were divided into a discovery cohort of 179 cases in comparison with 1,917 control subjects and a replication cohort of 109 cases and 1,114 control subjects.ResultsOur analyses detected strong association with the MHC region and association with a disintegrin and metalloproteinase (ADAM) genes (P combined = 1.96 × 10(-7)) replicated in the independent cohort. CNV analysis defined 16 disease-associated deletions and duplications, including duplication of origin recognition complex 4L (ORC4L) that was unique to 15 cases (P = 8.66 × 10(-16)), as well as numerous unique rare intraexonic deletions and duplications suggesting multiple novel genetic causes of CVID. Furthermore, the 1,000 most significant SNPs were strongly predictive of the CVID phenotype by using a Support Vector Machine algorithm with positive and negative predictive values of 1.0 and 0.957, respectively.ConclusionOur integrative genome-wide analysis of SNP genotypes and CNVs has uncovered multiple novel susceptibility loci for CVID, both common and rare, which is consistent with the highly heterogeneous nature of CVID. These results provide new mechanistic insights into immunopathogenesis based on these unique genetic variations and might allow for improved diagnosis of CVID based on accurate prediction of the CVID clinical phenotypes by using our Support Vector Machine model.

| S-EPMC3646656 | biostudies-literature

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

Project description:Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

| S-EPMC3827979 | biostudies-literature

Genome wide association study identifies four loci for early onset schizophrenia.

Project description:Early onset schizophrenia (EOS, defined as first onset of schizophrenia before age 18) is a rare form of schizophrenia (SCZ). Though genome-wide association studies (GWASs) have identified multiple risk variants for SCZ, most of the cases included in these GWASs were not stratified according to their first age at onset. To date, the genetic architecture of EOS remains largely unknown. To identify the risk variants and to uncover the genetic basis of EOS, we conducted a two-stage GWAS of EOS in populations of Han Chinese ancestry in this study. We first performed a GWAS using 1,256 EOS cases and 2,661 healthy controls (referred as discovery stage). The genetic variants with a P < 1.0 × 10-04 in discovery stage were replicated in an independent sample (903 EOS cases and 3,900 controls). We identified four genome-wide significant risk loci for EOS in the combined samples (2,159 EOS cases and 6,561 controls), including 1p36.22 (rs1801133, Pmeta = 4.03 × 10-15), 1p31.1 (rs1281571, Pmeta = 4.14 × 10-08), 3p21.31 (rs7626288, Pmeta = 1.57 × 10-09), and 9q33.3 (rs592927, Pmeta = 4.01 × 10-11). Polygenic risk scoring (PRS) analysis revealed substantial genetic overlap between EOS and SCZ. These discoveries shed light on the genetic basis of EOS. Further functional characterization of the identified risk variants and genes will help provide potential targets for therapeutics and diagnostics.

| S-EPMC8079394 | biostudies-literature

Genome-wide meta-analysis of common variant differences between men and women.

Project description:The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

| S-EPMC3471397 | biostudies-literature

Genome-wide association analysis identifies common variants influencing infant brain volumes.

Project description:Genome-wide association studies (GWAS) of adolescents and adults are transforming our understanding of how genetic variants impact brain structure and psychiatric risk, but cannot address the reality that psychiatric disorders are unfolding developmental processes with origins in fetal life. To investigate how genetic variation impacts prenatal brain development, we conducted a GWAS of global brain tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume (P=4.15 × 10-10). An intronic SNP in WWOX (rs10514437) neared genome-wide significance for white matter volume (P=1.56 × 10-8). Additional loci with small P-values included psychiatric GWAS associations and transcription factors expressed in developing brain. Genetic predisposition scores for schizophrenia and ASD, and the number of genes impacted by rare copy number variants (CNV burden) did not predict global brain tissue volumes. Integration of these results with large-scale neuroimaging GWAS in adolescents (PNC) and adults (ENIGMA2) suggests minimal overlap between common variants impacting brain volumes at different ages. Ultimately, by identifying genes contributing to adverse developmental phenotypes, it may be possible to adjust adverse trajectories, preventing or ameliorating psychiatric and developmental disorders.

| S-EPMC5611727 | biostudies-literature

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Project description:Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

| S-EPMC7116623 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data