Dataset Information

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

ABSTRACT: Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61?887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

SUBMITTER: Ikeda M

PROVIDER: S-EPMC5822448 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Ikeda M M Takahashi A A Kamatani Y Y Okahisa Y Y Kunugi H H Mori N N Sasaki T T Ohmori T T Okamoto Y Y Kawasaki H H Shimodera S S Kato T T Yoneda H H Yoshimura R R Iyo M M Matsuda K K Akiyama M M Ashikawa K K Kashiwase K K Tokunaga K K Kondo K K Saito T T Shimasaki A A Kawase K K Kitajima T T Matsuo K K Itokawa M M Someya T T Inada T T Hashimoto R R Inoue T T Akiyama K K Tanii H H Arai H H Kanba S S Ozaki N N Kusumi I I Yoshikawa T T Kubo M M Iwata N N

Molecular psychiatry 20170124 3

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10<sup>-9</sup>), a region known to contain regulatory genes for plasma lipid leve ...[more]

PMID: 28115744

Similar Datasets

Project description:ObjectivesRecent 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.MethodsA 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.ResultsAssociations 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.ConclusionsThese 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

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Publications

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets