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The association between antibodies to neurotropic pathogens and bipolar disorder : A study in the Dutch Bipolar (DB) Cohort and meta-analysis.

ABSTRACT: Exposure to neurotropic pathogens has been hypothesized to be a risk factor for the development of bipolar disorder (BD). However, evidence so far is inconsistent. We, therefore, analyzed the seroprevalence and titer levels of IgG antibodies against several herpesviruses and Toxoplasma gondii (T. gondii) in plasma of 760 patients with a bipolar disorder, 144 first-degree matched relatives and 132 controls of the Dutch Bipolar (DB) Cohort using ELISA. In addition, we performed a literature-based meta-analysis on the seroprevalence of IgG antibodies against these pathogens (n?=?14). Our results in the DB Cohort and subsequent meta-analysis (n?=?2364 BD patients, n?=?5101 controls) show no association between exposure to herpesviruses and bipolar disorder (HSV-1 [adjusted OR 0.842, 95% CI 0.567-1.230], HSV-2 [adjusted OR 0.877, 95% CI 0.437-1.761], CMV [adjusted OR 0.884 95% CI 0.603-1.295], EBV [adjusted OR 0.968 95% CI 0.658-1.423]). In the DB Cohort, we did not find an association between bipolar disorder and T. gondii titer or seroprevalence either [adjusted OR 1.018, 95% CI 0.672-1.542]. The overall OR was not significant for T. gondii [OR: 1.4, 95% CI 0.95-1.90, p?=?0.09), but subgroup analyses in age groups below 40 years showed a significantly increased seroprevalence of T. gondii IgGs in BD [OR: 1.8 (95% CI 1.10-2.89, p?=?0.021]. Our meta-analysis indicates that T. gondii exposure may be a risk factor for BD in certain subpopulations.

SUBMITTER: Snijders GJLJ

PROVIDER: S-EPMC6868237 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The association between antibodies to neurotropic pathogens and bipolar disorder : A study in the Dutch Bipolar (DB) Cohort and meta-analysis.

Snijders Gijsje J L J GJLJ van Mierlo Hans C HC Boks Marco P MP Begemann Marieke J H MJH Sutterland Arjen L AL Litjens Manja M Ophoff Roel A RA Kahn René S RS de Witte Lot D LD

Translational psychiatry 20191120 1

Exposure to neurotropic pathogens has been hypothesized to be a risk factor for the development of bipolar disorder (BD). However, evidence so far is inconsistent. We, therefore, analyzed the seroprevalence and titer levels of IgG antibodies against several herpesviruses and Toxoplasma gondii (T. gondii) in plasma of 760 patients with a bipolar disorder, 144 first-degree matched relatives and 132 controls of the Dutch Bipolar (DB) Cohort using ELISA. In addition, we performed a literature-based ...[more]

PMID: 31748521

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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

The association between antibodies to neurotropic pathogens and bipolar disorder : A study in the Dutch Bipolar (DB) Cohort and meta-analysis.

Publications

The association between antibodies to neurotropic pathogens and bipolar disorder : A study in the Dutch Bipolar (DB) Cohort and meta-analysis.

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