Dataset Information

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

ABSTRACT: Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n?=?328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75×10(-6) and 8.3×10(-7). Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of causal variants and their functional effects may unveil yet unknown players in the neurodevelopment and the pathogenesis of neuropsychiatric disorders.

SUBMITTER: Hass J

PROVIDER: S-EPMC3689744 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

Hass Johanna J Walton Esther E Kirsten Holger H Liu Jingyu J Priebe Lutz L Wolf Christiane C Karbalai Nazanin N Gollub Randy R White Tonya T Roessner Veit V Müller Kathrin U KU Paus Tomas T Smolka Michael N MN Schumann Gunter G Scholz Markus M Cichon Sven S Calhoun Vince V Ehrlich Stefan S

PloS one 20130621 6

Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we ...[more]

PMID: 23805179

Similar Datasets

Project description:Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7-10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5×10(-8) in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65×10(-9), OR = 1.29, CI = 1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70×10(-8), OR = 1.20, Cl = 1.13-1.29, and rs6757804; P = 4.05×10(-8), OR = 1.20, Cl = 1.13-1.29). Using an adjusted Bonferoni significance threshold of 4.51×10(-7) we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19×10(-7), OR = 1.20, Cl = 1.12-1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08×10(-7), OR = 1.19, Cl = 1.11-1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.

Dataset Information

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

Publications

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets