title: Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes.
abstract: 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.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Switzerland.
authors.forename: Federico A
authors.initials: FA
authors.lastname: Santoni
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, West Virginia, United States of America.
authors.forename: Vincent
authors.initials: V
authors.lastname: Setola
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Gehrig
authors.affiliation: Centre Hospitalier du Rouvray, Sotteville les Rouen et INSERM U1079, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Rotharmel
authors.affiliation: Centre Hospitalier du Rouvray, Sotteville les Rouen et INSERM U1079, France.
authors.forename: Macarena
authors.initials: M
authors.lastname: Cuenca
authors.affiliation: Centre Hospitalier du Rouvray, Sotteville les Rouen et INSERM U1079, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillin
authors.affiliation: 1st Department of Psychiatry at the Athens University Medical School, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Dikeos
authors.affiliation: 1st Department of Psychiatry at the Athens University Medical School, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Georgantopoulos
authors.affiliation: 1st Department of Psychiatry at the Athens University Medical School, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Papadimitriou
authors.affiliation: Department of Mental Health and Psychiatry, Geneva, Switzerland.
authors.forename: Logos
authors.initials: L
authors.lastname: Curtis
authors.affiliation: Inserm U955, Psychiatrie Génétique, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital A. Chenevier - H. Mondor, Pôle de Psychiatrie, Créteil, France; Fondation Fondamental, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Méary
authors.affiliation: Inserm U955, Psychiatrie Génétique, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital A. Chenevier - H. Mondor, Pôle de Psychiatrie, Créteil, France; Fondation Fondamental, Créteil, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Schürhoff
authors.affiliation: Inserm U955, Psychiatrie Génétique, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital A. Chenevier - H. Mondor, Pôle de Psychiatrie, Créteil, France; Fondation Fondamental, Créteil, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jamain
authors.affiliation: Epidemiology and Genetics Program in Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Avramopoulos
authors.affiliation: Inserm U955, Psychiatrie Génétique, Créteil, France; Université Paris Est, Faculté de Médecine, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital A. Chenevier - H. Mondor, Pôle de Psychiatrie, Créteil, France; Fondation Fondamental, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: Department of Psychiatry, University of Halle, Halle, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: Epidemiology and Genetics Program in Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Pulver
authors.affiliation: Centre Hospitalier du Rouvray, Sotteville les Rouen et INSERM U1079, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, West Virginia, United States of America.
authors.forename: David P
authors.initials: DP
authors.lastname: Siderovski
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), Geneva, Switzerland.
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D022821:RNA Splice Sites / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D022821:RNA Splice Sites