Identification of novel loci for bipolar I disorder in a multi-stage genome-wide association study

Identification of genetic variants that influence bipolar I disorder (BPD-I) through genome-wide association (GWA) studies is limited in Asian populations. The current study aimed to identify novel common variants for BPD-I in an ethnically homogeneous Taiwanese sample using a multi-stage GWA study...

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Bibliographic Details
Published in:Progress in neuro-psychopharmacology & biological psychiatry 2014-06, Vol.51, p.58-64
Main Authors: Kuo, P.H., Chuang, L.C., Liu, J.R., Liu, C.M., Huang, M.C., Lin, S.K., Sunny Sun, H., Hsieh, M.H., Hung, H., Lu, R.B.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Adult and adolescent clinical studies
Aged
Biological and medical sciences
Bipolar disorder
Bipolar Disorder - genetics
Bipolar disorders
Ether-A-Go-Go Potassium Channels - genetics
Female
Genetic Predisposition to Disease - genetics
Genome-wide association
Genome-Wide Association Study
Genotype
Histone Acetyltransferases - genetics
Humans
Logistic Models
Male
Medical sciences
Middle Aged
Mood disorders
Nerve Tissue Proteins - genetics
Neuropharmacology
Pharmacology. Drug treatments
Polymorphism, Single Nucleotide - genetics
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Rank-based method
Semaphorins - genetics
Taiwan
Young Adult
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Summary:Identification of genetic variants that influence bipolar I disorder (BPD-I) through genome-wide association (GWA) studies is limited in Asian populations. The current study aimed to identify novel common variants for BPD-I in an ethnically homogeneous Taiwanese sample using a multi-stage GWA study design. At the discovery stage, 200 BPD-I patients and 200 controls that combined to form 16 pools were genotyped with 1million markers. Utilizing a newly developed rank-based method, top-ranked markers were selected. After validation with individual genotyping, a fine-mapping association study was conducted to identify associated loci using 240 patients and 240 controls. At the last stage, independent samples were collected (351 cases and 341 controls) for replication. Among the top-ranked markers from the discovery stage, eight genes and 15 individual SNPs were evaluated in the fine-mapping stage. At this stage, rs7619173, which is not in a gene coding region, showed the most significant association (P=2∗10−5) with BPD-I. Four genes had empirical P-values
ISSN:0278-5846
1878-4216
DOI:10.1016/j.pnpbp.2014.01.003