Cumulative effect of the plasma total homocysteine-related genetic variants on schizophrenia risk.
Previous studies suggest that elevated total homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which correlates with plasma total homocysteine levels, are risk factors for schizophrenia (SCZ). Recently, a large genome-wide association study (GWAS) of plasma total homocysteine levels in individuals of European ancestry identified many single-nucleotide polymorphisms (SNPs) (n=13,974). The primary purpose of this study was to examine the association between these plasma total homocysteine-related SNPs and SCZ in the Japanese population. First, we investigated associations between six SNPs and plasma total homocysteine levels in non-psychiatric subjects in the Japanese population (n=1030). Then, we evaluated the cumulative effects of three SNPs on SCZ risk by calculating the Genotype Risk Score (GRS) (1120 cases, 2643 controls). Of the six SNPs examined, we replicated similar associations with the European GWAS at four loci (CENPQ, CPS1, MTHFR, and MUT). GRS based on three SNPs (CENPQ, CPS1, and MTHFR) was significantly associated with SCZ. Our findings suggest that common polygenic variations, which are associated with the plasma total homocysteine levels, may contribute to the risk of SCZ.
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Makoto
M
Kinoshita
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan. Electronic address: shu-numata@umin.ac.jp.
Shusuke
S
Numata
Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical, Sciences, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa 920-8640, Japan; Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Atsushi
A
Tajima
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Akira
A
Nishi
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Sho
S
Muraki
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Atsushi
A
Tsuchiya
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Hidehiro
H
Umehara
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Shin-Ya
SY
Watanabe
Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Issei
I
Imoto
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima 770-8503, Japan.
Tetsuro
T
Ohmori
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology
D015415:Biomarkers; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
Case-control association study; Genotype risk score; Single nucleotide polymorphism