Dataset Information

PS3-15: Genome-Wide Association Study of Anxiety Disorders: Early Results from Kaiser Permanente’s Research Program on Genes, Environment, and Health (RPGEH)

ABSTRACT:

Background/Aims

The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging (GERA) cohort includes 110,266 individuals with comprehensive longitudinal medical records along with genome-wide genotype data. As such, it provides an unprecedented opportunity to conduct a number of genome-wide association studies (GWAS) of psychiatric disorders. Post-traumatic stress disorder (PTSD) and panic disorder (PD) are prevalent, persistent, disabling and heritable anxiety disorders. Numerous candidate gene studies have been published with inconsistent findings. We conducted the GWAS of PTSD and the GWAS of panic disorder among non-Hispanic white GERA cohorts to detect the underlying heterogeneous genetic architecture.

Methods

We identified a total of 6177 combined ASD and PTSD cases in the GERA cohort, in which cases had two or more psychiatric diagnoses of ASD and/or PTSD; the GERA cohort supplied 63,613 controls. A total of 1483 subjects with two or more diagnoses of panic disorder and 75,379 controls were included in the GWAS of panic disorder. All the cases and controls were genotyped on the custom Affymetrix Axiom EUR arrays with 674,518 SNPs.

Results

In the GWAS of combined ASD and PTSD or the GWAS of PD, a suggestive association with ASD/PTSD was found with a SNP in an intergenic region on chromosome 10 near the ANKRD20A gene (OR = 1.11, P = 1.42×10?7), as well as neighboring SNPs. In the GWAS of PD, we replicated a SNP association (rs1873727) in intron 3 of TMEM132D which was reported in a recent GWAS of PD.

Conclusions

Our analysis did not yield conclusive associations with PTSD or PD. We replicated a candidate gene in TMEM132D in the PD analysis. This suggests that we can observe true association signals for these disorders, but additional cases are needed to detect modest effects. GWAS of psychiatric disorders remain challenging.

SUBMITTER: Shen L

PROVIDER: S-EPMC3788382 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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