title: Investigation of endocannabinoid system genes suggests association between peroxisome proliferator activator receptor-α gene (PPARA) and schizophrenia.
abstract: Schizophrenia (SZ) is a complex psychiatric disorder with a large genetic burden and an estimated hereditability of 80%. A large number of neuroanatomical and psychopharmacological studies suggest a central role of the endocannabinoid (eCB) system in the susceptibility of the disease. To further investigate this hypothesis, we performed an association study with genes codifying for key elements of the eCB system in a sample of 170 schizophrenic patients and 350 healthy controls of Italian ancestry. A total of 57 Tag SNPs (tSNPs) were selected using HapMap CEU population SNP database spanning the following genes: cannabinoid receptor 1 (CNR1), peroxisome proliferator activator receptor-α (PPARA), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p<0.05). The same pattern of association was observed in the genotype analysis, with rs4253765 showing the highest level of significance (uncorrected p=2×10(-3)). None of these associations survived after permutation test. Our findings suggest a potential role for PPARA in the susceptibility to SZ, but further studies on larger independent samples are warranted in order to clarify the involvement of this gene in the pathophysiology of SZ.
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Costa
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Paola
authors.initials: P
authors.lastname: Niola
authors.forename: Silvana
authors.initials: S
authors.lastname: Galderisi
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000328:Adult; D030541:Databases, Genetic; D063388:Endocannabinoids / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D063388:Endocannabinoids; D047493:PPAR alpha