Dataset Information

Further Evidence of an Association between NCAN rs1064395 and Bipolar Disorder.

ABSTRACT: Genome-wide association studies suggest that rs1064395 in the neurocan gene (NCAN) is a potential risk factor for bipolar disorder (BPD), and further replication analyses in larger independent samples are needed. We herein analyzed rs1064395 in a Han Chinese sample of 1,146 BPD cases and 2,031 controls, followed by a meta-analysis of BPD samples from worldwide populations including a total of 15,318 cases and 91,990 controls. The meta-analysis found that rs1064395 showed a genome-wide significant association with BPD (p = 4.92 × 10-9, OR = 1.126 for the A allele), although it did not reach the significance level in the Han Chinese sample (p = 0.415, OR = 1.070 for the A allele). We also examined the association between the single nucleotide polymorphisms and major depressive disorder (MDD) given the presumed genetic overlap between BPD and MDD, and rs1064395 was also associated with MDD (p = 0.0068, OR = 1.067 for the A allele) in a meta-analysis of 14,543 cases and 14,856 controls. Our data provide further evidence for the involvement of NCAN in the genetic susceptibility to BPD and also implicate its broader role in major mood disorders.

SUBMITTER: Wang L

PROVIDER: S-EPMC6032033 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Further Evidence of an Association between <i>NCAN</i> rs1064395 and Bipolar Disorder.

Wang Lu L Liu Weiqing W Li Xingxing X Xiao Xiao X Li Lingyi L Liu Fang F He Yuanfang Y Bai Yan Y Chang Hong H Zhou Dong-Sheng DS Li Ming M

Molecular neuropsychiatry 20180517 1

Genome-wide association studies suggest that rs1064395 in the neurocan gene (<i>NCAN</i>) is a potential risk factor for bipolar disorder (BPD), and further replication analyses in larger independent samples are needed. We herein analyzed rs1064395 in a Han Chinese sample of 1,146 BPD cases and 2,031 controls, followed by a meta-analysis of BPD samples from worldwide populations including a total of 15,318 cases and 91,990 controls. The meta-analysis found that rs1064395 showed a genome-wide sig ...[more]

PMID: 29998116

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Project description:BackgroundBipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB.MethodsWe genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching.ResultsWe report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs.ConclusionOur findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.

Dataset Information

Further Evidence of an Association between NCAN rs1064395 and Bipolar Disorder.

Publications

Further Evidence of an Association between <i>NCAN</i> rs1064395 and Bipolar Disorder.

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