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

• Published in: Schizophrenia research 2008-09, Vol.104 (1), p.153-164
• Main Authors: Takahashi, Sakae, Cui, Yu-hu, Han, Yong-hua, Fagerness, Jesen A, Galloway, Brian, Shen, Yu-cun, Kojima, Takuya, Uchiyama, Makoto, Faraone, Stephen V, Tsuang, Ming T
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; African Americans - genetics; AOPL2; APOL gene family cluster; APOL1; APOL4; Apolipoprotein L1; Apolipoproteins - genetics; Apolipoproteins L; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Chromosome 22; Chromosomes, Human, Pair 22 - genetics; European Continental Ancestry Group - genetics; Gene Frequency; Genotype; Haplotypes - genetics; Humans; Lipoproteins, HDL - genetics; Medical sciences; Polymorphism, Single Nucleotide - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - ethnology; Schizophrenia - genetics
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2008.05.028

Abstract Prior work found the APOL1, 2 and 4 genes, located on chromosome 22q12.3–q13.1, to be upregulated 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.