title: Meta-analysis of genome-wide association studies for panic disorder in the Japanese population.
abstract: Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Otowa
authors.forename: Y
authors.initials: Y
authors.lastname: Kawamura
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: N
authors.initials: N
authors.lastname: Sugaya
authors.forename: A
authors.initials: A
authors.lastname: Koike
authors.forename: E
authors.initials: E
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
authors.forename: F
authors.initials: F
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Kuwabara
authors.forename: M
authors.initials: M
authors.lastname: Tochigi
authors.forename: C
authors.initials: C
authors.lastname: Kakiuchi
authors.forename: T
authors.initials: T
authors.lastname: Umekage
authors.forename: T
authors.initials: T
authors.lastname: Miyagawa
authors.forename: A
authors.initials: A
authors.lastname: Miyashita
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Akiyoshi
authors.forename: T
authors.initials: T
authors.lastname: Someya
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: R
authors.initials: R
authors.lastname: Kuwano
authors.forename: K
authors.initials: K
authors.lastname: Kasai
authors.forename: N
authors.initials: N
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Kaiya
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Okazaki
authors.forename: H
authors.initials: H
authors.lastname: Tanii
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D016584:Panic Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide