TY - JOUR
T1 - Novel missense SETD1A variants in Japanese patients with schizophrenia
T2 - Resequencing and association analysis
AU - Morikawa, Ryo
AU - Watanabe, Yuichiro
AU - Igeta, Hirofumi
AU - Arta, Reza K.
AU - Ikeda, Masashi
AU - Okazaki, Satoshi
AU - Hoya, Satoshi
AU - Saito, Takeo
AU - Otsuka, Ikuo
AU - Egawa, Jun
AU - Tanifuji, Takaki
AU - Iwata, Nakao
AU - Someya, Toshiyuki
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - SETD1A has been identified as a substantial risk gene for schizophrenia. To further investigate the role of SETD1A in the genetic etiology of schizophrenia in the Japanese population, we performed resequencing and association analyses. First, we resequenced the SETD1A coding regions of 974 patients with schizophrenia. Then, we genotyped variants, prioritized via resequencing, in 2,027 patients with schizophrenia and 2,664 controls. Next, we examined the association between SETD1A and schizophrenia in 3,001 patients with schizophrenia and 2,664 controls. Finally, we performed a retrospective chart review of patients with prioritized SETD1A variants. We identified two novel missense variants (p.Ser575Pro and p.Glu857Gln) via resequencing. We did not detect these variants in 4,691 individuals via genotyping. These variants were not significantly associated with schizophrenia in the association analysis. Additionally, we found that a schizophrenia patient with the p.Glu857Gln variant had developmental delays. In conclusion, novel SETD1A missense variants were exclusively identified in Japanese patients with schizophrenia. However, our study does not provide evidence for the contribution of these variants to the genetic etiology of schizophrenia in the Japanese population.
AB - SETD1A has been identified as a substantial risk gene for schizophrenia. To further investigate the role of SETD1A in the genetic etiology of schizophrenia in the Japanese population, we performed resequencing and association analyses. First, we resequenced the SETD1A coding regions of 974 patients with schizophrenia. Then, we genotyped variants, prioritized via resequencing, in 2,027 patients with schizophrenia and 2,664 controls. Next, we examined the association between SETD1A and schizophrenia in 3,001 patients with schizophrenia and 2,664 controls. Finally, we performed a retrospective chart review of patients with prioritized SETD1A variants. We identified two novel missense variants (p.Ser575Pro and p.Glu857Gln) via resequencing. We did not detect these variants in 4,691 individuals via genotyping. These variants were not significantly associated with schizophrenia in the association analysis. Additionally, we found that a schizophrenia patient with the p.Glu857Gln variant had developmental delays. In conclusion, novel SETD1A missense variants were exclusively identified in Japanese patients with schizophrenia. However, our study does not provide evidence for the contribution of these variants to the genetic etiology of schizophrenia in the Japanese population.
KW - Developmental delay
KW - Genotyping
KW - Rare variant
KW - SETD1A
KW - Schizophrenia
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U2 - 10.1016/j.psychres.2022.114481
DO - 10.1016/j.psychres.2022.114481
M3 - Article
C2 - 35235885
AN - SCOPUS:85125246346
SN - 0165-1781
VL - 310
JO - Psychiatry Research
JF - Psychiatry Research
M1 - 114481
ER -