Rare FBXO18 variations and risk of schizophrenia: Whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies.
OBJECTIVE
Rare variations are suggested to play a role in the genetic etiology of schizophrenia; to further investigate their role, we performed a three-stage study in a Japanese population.


METHODS
In the first stage, we performed whole-exome sequencing (WES) of two parent-affected offspring trios. In the second stage, we resequenced the FBXO18 coding region in 96 patients. In the third stage, we tested rare non-synonymous FBXO18 variations for association with schizophrenia in two independent populations comprising a total of 1376 patients and 1496 controls.


RESULTS
A rare frameshift variation (L116fsX) in the FBXO18 gene was recurrently identified by WES in both trios. Resequencing FBXO18 coding regions, we detected three rare non-synonymous variations (V15L, L116fsX, and V1006I). However, there were no significant associations between these rare FBXO18 variations and schizophrenia in the case-control study.


CONCLUSIONS
Our present study does not provide evidence for the contribution of rare non-synonymous FBXO18 variations to the genetic etiology of schizophrenia in the Japanese population. However, to draw a definitive conclusion, further studies should be performed using sufficiently large sample sizes.
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Satoshi
S
Hoya
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Department of Psychiatry, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Japan.
Yuichiro
http://orcid.org/0000-0002-5496-5997
Y
Watanabe
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Akitoyo
A
Hishimoto
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Oojima Hospital, Sanjo, Japan.
Ayako
A
Nunokawa
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Emiko
E
Inoue
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Hirofumi
H
Igeta
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Ikuo
I
Otsuka
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Medical Education, Comprehensive Medical Education Center, School of Medicine, Faculty of Medicine, Niigata University, Niigata, Japan.
Masako
M
Shibuya
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Jun
J
Egawa
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Ichiro
I
Sora
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Toshiyuki
T
Someya
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*; D000073359:Exome Sequencing
D004268:DNA-Binding Proteins; D004265:DNA Helicases; C464443:FBH1 protein, human
FBXO18; Japanese; rare variation; schizophrenia; whole-exome sequencing