Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 824-834 |
| Number of pages | 11 |
| Journal | Schizophrenia Bulletin |
| Volume | 45 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Psychiatry and Mental health
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Genome-wide association study detected novel susceptibility genes for schizophrenia and shared trans-populations/diseases genetic effect. / Ikeda, Masashi; Takahashi, Atsushi; Kamatani, Yoichiro; Momozawa, Yukihide; Saito, Takeo; Kondo, Kenji; Shimasaki, Ayu; Kawase, Kohei; Sakusabe, Takaya; Iwayama, Yoshimi; Toyota, Tomoko; Wakuda, Tomoyasu; Kikuchi, Mitsuru; Kanahara, Nobuhisa; Yamamori, Hidenaga; Yasuda, Yuka; Watanabe, Yuichiro; Hoya, Satoshi; Aleksic, Branko; Kushima, Itaru; Arai, Heii; Takaki, Manabu; Hattori, Kotaro; Kunugi, Hiroshi; Okahisa, Yuko; Ohnuma, Tohru; Ozaki, Norio; Someya, Toshiyuki; Hashimoto, Ryota; Yoshikawa, Takeo; Kubo, Michiaki; Iwata, Nakao.
In: Schizophrenia Bulletin, Vol. 45, No. 4, 01.01.2019, p. 824-834.Research output: Contribution to journal › Article
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
PY - 2019/1/1
Y1 - 2019/1/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=85068479502&partnerID=8YFLogxK
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 -