Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia.
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.
Takahashi
Sakae
S
Division of Psychiatry, Department of Psychiatry, Nihon University, School of Medicine, Tokyo, Japan.
Cui
Yu-hu
YH
Han
Yong-hua
YH
Fagerness
Jesen A
JA
Galloway
Brian
B
Shen
Yu-cun
YC
Kojima
Takuya
T
Uchiyama
Makoto
M
Faraone
Stephen V
SV
Tsuang
Ming T
MT
D001741:Black or African American / Q000235:genetics; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D000075943:Apolipoproteins L; D044466:Asian People / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics
C108666:APOL1 protein, human; C543112:APOL2 protein, human; C543113:APOL4 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D000075943:Apolipoproteins L; D008075:Lipoproteins, HDL