論文

査読有り 国際誌
2019年6月18日

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

Schizophrenia bulletin
  • Masashi Ikeda
  • Atsushi Takahashi
  • Yoichiro Kamatani
  • Yukihide Momozawa
  • Takeo Saito
  • Kenji Kondo
  • Ayu Shimasaki
  • Kohei Kawase
  • Takaya Sakusabe
  • Yoshimi Iwayama
  • Tomoko Toyota
  • Tomoyasu Wakuda
  • Mitsuru Kikuchi
  • Nobuhisa Kanahara
  • Hidenaga Yamamori
  • Yuka Yasuda
  • Yuichiro Watanabe
  • Satoshi Hoya
  • Branko Aleksic
  • Itaru Kushima
  • Heii Arai
  • Manabu Takaki
  • Kotaro Hattori
  • Hiroshi Kunugi
  • Yuko Okahisa
  • Tohru Ohnuma
  • Norio Ozaki
  • Toshiyuki Someya
  • Ryota Hashimoto
  • Takeo Yoshikawa
  • Michiaki Kubo
  • Nakao Iwata
  • 全て表示

45
4
開始ページ
824
終了ページ
834
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/schbul/sby140

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 54479 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.

リンク情報
DOI
https://doi.org/10.1093/schbul/sby140
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30285260
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581133
ID情報
  • DOI : 10.1093/schbul/sby140
  • ISSN : 0586-7614
  • PubMed ID : 30285260
  • PubMed Central 記事ID : PMC6581133

エクスポート
BibTeX RIS