Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect

被引：98

作者：

Ikeda, Masashi ^{[1
]}

Takahashi, Atsushi ^{[2
,3
]}

Kamatanim, Yoichiro ^{[2
,4
]}

Momozawa, Yukihide ^{[5
]}

Saito, Takeo ^{[1
]}

Kondo, Kenji ^{[1
]}

Shimasaki, Ayu ^{[1
]}

Kawase, Kohei ^{[1
]}

Sakusabe, Takaya ^{[6
]}

Iwayama, Yoshimi ^{[7
]}

Toyota, Tomoko ^{[7
]}

Wakudas, Tomoyasu ^{[8
]}

Kikuchi, Mitsuru ^{[9
]}

Kanahara, Nobuhisa ^{[10
]}

Yamamori, Hidenaga ^{[11
]}

Yasuda, Yuka ^{[11
]}

Watanabe, Yuichiro ^{[12
]}

Hoya, Satoshi ^{[12
]}

Aleksic, Branko ^{[13
]}

Kushima, Itaru ^{[13
]}

Arai, Heii ^{[14
]}

Takaki, Manabu ^{[15
]}

Hattori, Kotaro ^{[16
]}

Kurrugi, Hiroshi ^{[15
]}

Okahisa, Yuko ^{[15
]}

Ohnuma, Tohru ^{[14
]}

Ozaki, Norio ^{[13
]}

Someya, Toshiyuki ^{[12
]}

Hashimotovs, Ryota ^{[17
,18
]}

Yoshikawa, Takeo ^{[7
]}

Kubo, Michiaki ^{[19
]}

Iwata, Nakao ^{[1
]}

机构：

[1] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan

[2] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[3] Natl Cerebral & Cardiovasc Ctr, Dept Genom Med, Res Inst, Osaka, Japan

[4] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[5] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[6] Fujita Hlth Univ, Sch Hlth Sci, Fac Clin Engn, Toyoake, Aichi, Japan

[7] RIKEN, Ctr Brain Sci, Lab Mol Psychiat, Wako, Saitama, Japan

[8] Hamamatsu Univ Sch Med, Dept Psychiat, Hamamatsu, Shizuoka, Japan

[9] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa, Japan

[10] Chiba Univ, Grad Sch Med, Dept Psychiat, Chiba, Japan

[11] Osaka Univ, Grad Sch Med, Dept Psychiat, Suita, Osaka, Japan

[12] Niigata Univ, Grad Sch Med & Dent Sci, Dept Psychiat, Niigata, Japan

[13] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi, Japan

[14] Juntendo Univ, Fac Med, Dept Psychiat, Tokyo, Japan

[15] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neuropsychiat, Okayama, Japan

[16] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Tokyo, Japan

[17] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Pathol Mental Dis, Tokyo, Japan

[18] Osaka Univ, Suita, Osaka, Japan

[19] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

来源：

SCHIZOPHRENIA BULLETIN | 2019年 / 45卷 / 04期

基金：

日本学术振兴会;

关键词：

polygenic score; SLC38A; SPHKAP; CABP1; ACADS; GWAS; IDENTIFIES; 2; RISK LOCI; POLYGENICITY; INDIVIDUALS; GLUTAMATE; PROTEIN;

D O I：

10.1093/schbul/sby140

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Genome-wide association studies (GWASs) have identified >1(M) 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 WAS' 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 (transdiseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (P-best = 4.1 x 10(-10)), SLC38A3 (P-best = 5.7 x 10(-10)), and CABP1-ACADS (P-best = 9.8 x 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 (P-best = 4.0 x 10(-11)) and between SCZ and BD in the JPN population (P similar to 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 rho = 0.58, whereas a similar/lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, r(g) = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, rho = 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.

引用

页码：824 / 834

页数：11

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