Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia

SCHIZOPHRENIA RESEARCH

卷:104

Article

Takahashi, Sakae²  Cui, Yu-hu¹¹  Han, Yong-hua¹¹  Fagerness, Jesen A.^9,10  Galloway, Brian^9,10  Shen, Yu-cun¹¹  Kojima, Takuya²  Uchiyama, Makoto²  Faraone, Stephen V.⁸  Tsuang, Ming T.^1,3,4,5,6,7 

[1] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA

[2] Nihon Univ, Sch Med, Dept Psychiat, Div Psychiat, Tokyo, Japan

[3] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA

[5] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA

[6] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[7] Univ Calif San Diego, San Diego, CA 92103 USA

[8] SUNY Upstate Med Univ, Dept Psychiat & Neurosci & Physiol, Syracuse, NY USA

[9] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA

[10] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA

[11] Peking Univ, Inst Mental Hlth, Beijing, Peoples R China

关键词: schizophrenia;    chromosome 22;    APOL gene family cluster;    APOL1;    AOPL2;    APOL4;   

DOI  :  10.1016/j.schres.2008.05.028

来源: Elsevier

【 摘 要 】

Prior work found the A POL1, 2 and 4 genes, located on chromosome 22q12.3-q113.1, to be upreaulated in brains of schizophrenic patients, We performed a family-based association study using 130 SNPs tagging the APOL gene family (APOL1-6). The Subjects were 112 African-American (AA), 114 European-American (EA), 109 Chinese (Ch) and 42 Japanese (Jp) families with schizophrenia (377 families, 1161 genotyped members and 647 genotyped affected in total). Seven SNPs had p-values< 0.05 in the APOL1, 2 and 4 regions for the AA, EA and combined (AA and EA) samples. In the AA sample, two SNPs, rs9610449 and rs6000200 showed low p-values; and a haplotype which comprised these two SNPs yielded a p-value of 0.00029 using the global test (GT) and the allele specific test (AST). The two SNPs and the haplotype were associated with risk for schizophrenia in African-Americans. In the combined (AA and EA) sample, two SNPs, rs2003813 and rs2157249 showed low p-values; and a three SNP haplotype including these two SNPs was significant using the GT (p = 0.0013) and the AST (p = 0.000090). The association of this haplotype with schizophrenia was significant for the entire (AA, EA, Ch and Jp) sample using the GT (p = 0.00054) and the AST (p = 0.00011). Although our study is not definitive, it suggests that the APOL genes should be more extensively studied in schizophrenia, (C) 2008 Elsevier B.V. All rights reserved.

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