Dataset Information

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

ABSTRACT: We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.

SUBMITTER: Cichon S

PROVIDER: S-EPMC3059436 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

Cichon Sven S Mühleisen Thomas W TW Degenhardt Franziska A FA Mattheisen Manuel M Miró Xavier X Strohmaier Jana J Steffens Michael M Meesters Christian C Herms Stefan S Weingarten Moritz M Priebe Lutz L Haenisch Britta B Alexander Michael M Vollmer Jennifer J Breuer René R Schmäl Christine C Tessmann Peter P Moebus Susanne S Wichmann H-Erich HE Schreiber Stefan S Müller-Myhsok Bertram B Lucae Susanne S Jamain Stéphane S Leboyer Marion M Bellivier Frank F Etain Bruno B Henry Chantal C Kahn Jean-Pierre JP Heath Simon S Hamshere Marian M O'Donovan Michael C MC Owen Michael J MJ Craddock Nick N Schwarz Markus M Vedder Helmut H Kammerer-Ciernioch Jutta J Reif Andreas A Sasse Johanna J Bauer Michael M Hautzinger Martin M Wright Adam A Mitchell Philip B PB Schofield Peter R PR Montgomery Grant W GW Medland Sarah E SE Gordon Scott D SD Martin Nicholas G NG Gustafsson Omar O Andreassen Ole O Djurovic Srdjan S Sigurdsson Engilbert E Steinberg Stacy S Stefansson Hreinn H Stefansson Kari K Kapur-Pojskic Lejla L Oruc Liliana L Rivas Fabio F Mayoral Fermín F Chuchalin Alexander A Babadjanova Gulja G Tiganov Alexander S AS Pantelejeva Galina G Abramova Lilia I LI Grigoroiu-Serbanescu Maria M Diaconu Carmen C CC Czerski Piotr M PM Hauser Joanna J Zimmer Andreas A Lathrop Mark M Schulze Thomas G TG Wienker Thomas F TF Schumacher Johannes J Maier Wolfgang W Propping Peter P Rietschel Marcella M Nöthen Markus M MM

American journal of human genetics 20110225 3

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first f ...[more]

PMID: 21353194

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Project description:OBJECTIVES:Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. METHODS:A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. RESULTS:Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P?.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. CONCLUSIONS:These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.

Dataset Information

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

Publications

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

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