TY - JOUR
T1 - Genome-wide association study detected novel susceptibility genes for schizophrenia and shared trans-populations/diseases genetic effect
AU - Ikeda, Masashi
AU - Takahashi, Atsushi
AU - Kamatani, Yoichiro
AU - Momozawa, Yukihide
AU - Saito, Takeo
AU - Kondo, Kenji
AU - Shimasaki, Ayu
AU - Kawase, Kohei
AU - Sakusabe, Takaya
AU - Iwayama, Yoshimi
AU - Toyota, Tomoko
AU - Wakuda, Tomoyasu
AU - Kikuchi, Mitsuru
AU - Kanahara, Nobuhisa
AU - Yamamori, Hidenaga
AU - Yasuda, Yuka
AU - Watanabe, Yuichiro
AU - Hoya, Satoshi
AU - Aleksic, Branko
AU - Kushima, Itaru
AU - Arai, Heii
AU - Takaki, Manabu
AU - Hattori, Kotaro
AU - Kunugi, Hiroshi
AU - Okahisa, Yuko
AU - Ohnuma, Tohru
AU - Ozaki, Norio
AU - Someya, Toshiyuki
AU - Hashimoto, Ryota
AU - Yoshikawa, Takeo
AU - Kubo, Michiaki
AU - Iwata, Nakao
N1 - Funding Information:
This work was supported by the Strategic Research Program for Brain Sciences (SRPBS) from the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP18dm0107097, JP18dm0107087, JP18dm0107100, JP18dm0207005, and JP18dm0107083; part of the BioBank Japan Project from the Ministry of Education, Culture, Sports, and Technology (MEXT) of Japan; GRIFIN of P3GM from AMED under Grant Numbers JP18km0405201 and JP18km0405208; Japan Society for the Promotion of Science (JSPS) Kakenhi Grant Numbers JP25293253, JP16H05378, JP26293266, JP17H04251, and JP16K19785: Grant-in-Aid for Health Labour Sciences Research Grant from the Ministry of Health Labour and Welfare (Comprehensive Research on Disability Health and Welfare); Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/ MINDS) from AMED; Grant-in-Aid for Scientific Research on Innovative Areas, “Glial assembly: a new regulatory machinery of brain function and disorders” from MEXT; the Private University Research Branding Project from MEXT.
PY - 2019
Y1 - 2019
N2 - Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54 479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10−10), SLC38A3 (Pbest = 5.7 × 10−10), and CABP1-ACADS (Pbest = 9.8 × 10−9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10−11) and between SCZ and BD in the JPN population (P ~ 10−40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/ lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ “risk” effect is shared with other psychiatric disorders even across populations.
AB - Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54 479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10−10), SLC38A3 (Pbest = 5.7 × 10−10), and CABP1-ACADS (Pbest = 9.8 × 10−9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10−11) and between SCZ and BD in the JPN population (P ~ 10−40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/ lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ “risk” effect is shared with other psychiatric disorders even across populations.
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U2 - 10.1093/schbul/sby140
DO - 10.1093/schbul/sby140
M3 - Article
C2 - 30285260
AN - SCOPUS:85068479502
VL - 45
SP - 824
EP - 834
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
SN - 0586-7614
IS - 4
ER -