Genome-wide association study of bipolar I disorder in the Han Chinese population

• Published in: Molecular psychiatry Vol. 16; no. 5; pp. 548 - 556
• Main Authors: Lee, M T M, Chen, C H, Lee, C S, Chen, C C, Chong, M Y, Ouyang, W C, Chiu, N Y, Chuo, L J, Chen, C Y, Tan, H K L, Lane, H Y, Chang, T J, Lin, C H, Jou, S H, Hou, Y M, Feng, J, Lai, T J, Tung, C L, Chen, T J, Chang, C J, Lung, F W, Chen, C K, Shiah, I S, Liu, C Y, Teng, P R, Chen, K H, Shen, L J, Cheng, C S, Chang, T P, Li, C F, Chou, C H, Wang, K H T, Fann, C S J, Wu, J Y, Chen, Y T, Cheng, A T A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2011; Nature Publishing Group
• Subjects: 631/208/205/2138; 692/699/476/1333; 692/700/478/174; Adult and adolescent clinical studies; Ankyrins - genetics; Armed forces; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Bipolar disorder; Bipolar Disorder - epidemiology; Bipolar Disorder - ethnology; Bipolar Disorder - genetics; Bipolar disorders; Calcium channels (voltage-gated); Calcium Channels, L-Type - genetics; Chromosome 3; Consortia; Disease susceptibility; DNA-Binding Proteins - genetics; Female; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Hospitals; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Mood disorders; Neurosciences; Odds Ratio; original-article; Pathogenesis; Pharmacotherapy; Phenotype; Polymorphism, Single Nucleotide - genetics; Population studies; Potassium; Proteins - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychosis; Reproducibility of Results; Risk factors; Schizophrenia; Sialyltransferases - genetics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Transcription Factors - genetics; White people; Taiwan; China; bipolar genome study; Mood disorder; CACNB2; ST8SIA2; Chinese; Bipolar disorder; SP8; ANK3; KCTD12
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2010.43

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (
SP8
) and
ST8
α-
N
-acetyl- neuraminide α-2,8-sialyltransferase (
ST8SIA2
) are associated with Bipolar I, with
P
-values of 4.87 × 10
−7
(rs2709736) and 6.05 × 10
−6
(rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (
KCTD12
) (rs2073831,
P
=9.74 × 10
−6
) and in
CACNB2
(Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860,
P
=5.15 × 10
−5
), One SNP nearby the rs1938526 SNP of
ANK3
gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (
P
=6.55 × 10
−5
and
P
=1.48 × 10
−5
, respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.