TY - JOUR
T1 - Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes
AU - Guipponi, Michel
AU - Santoni, Federico A.
AU - Setola, Vincent
AU - Gehrig, Corinne
AU - Rotharmel, Maud
AU - Cuenca, Macarena
AU - Guillin, Olivier
AU - Dikeos, Dimitris
AU - Georgantopoulos, Georgios
AU - Papadimitriou, George
AU - Curtis, Logos
AU - Méary, Alexandre
AU - Schürhoff, Franck
AU - Jamain, Stéphane
AU - Avramopoulos, Dimitri
AU - Leboyer, Marion
AU - Rujescu, Dan
AU - Pulver, Ann
AU - Campion, Dominique
AU - Siderovski, David P.
AU - Antonarakis, Stylianos E.
N1 - Funding Information:
We are grateful to the members of all families enrolled in this study. We thank Dr. Diana Canovas and Prof. Alain Malafosse for patient recruitment. The computations were performed at the Vital-IT ( http://www.vital-it.ch ) Center for high-performance computing of the Swiss Institute of Bioinformatics (SIB). We thank the Swiss National Science Foundation (NCCR_Synapsy) for supporting the SEA laboratory. VS and DPS thank the Stanley Center for Psychiatry Research (Broad Institute, Cambridga, MA) for pilot funding. This work has been supported by INSERM, the Fondation FondaMental and the Labex Bio-Psy (Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02).
Publisher Copyright:
© 2014 Guipponi et al.
PY - 2014/11/24
Y1 - 2014/11/24
N2 - Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7 × 10-8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.
AB - Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7 × 10-8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.
UR - http://www.scopus.com/inward/record.url?scp=84912544206&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0112745
DO - 10.1371/journal.pone.0112745
M3 - Article
C2 - 25420024
AN - SCOPUS:84912544206
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e112745
ER -