title: Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1.
abstract: The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.
authors.affiliation: McLean Hospital, Belmont, Massachusetts, USA. evelyn.stewart@ubc.ca
authors.forename: S E
authors.initials: SE
authors.lastname: Stewart
authors.forename: C
authors.initials: C
authors.lastname: Mayerfeld
authors.forename: P D
authors.initials: PD
authors.lastname: Arnold
authors.forename: J R
authors.initials: JR
authors.lastname: Crane
authors.forename: C
authors.initials: C
authors.lastname: O'Dushlaine
authors.forename: J A
authors.initials: JA
authors.lastname: Fagerness
authors.forename: D
authors.initials: D
authors.lastname: Yu
authors.forename: J M
authors.initials: JM
authors.lastname: Scharf
authors.forename: E
authors.initials: E
authors.lastname: Chan
authors.forename: F
authors.initials: F
authors.lastname: Kassam
authors.forename: P R
authors.initials: PR
authors.lastname: Moya
authors.forename: J R
authors.initials: JR
authors.lastname: Wendland
authors.forename: R
authors.initials: R
authors.lastname: Delorme
authors.forename: M A
authors.initials: MA
authors.lastname: Richter
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: J
authors.initials: J
authors.lastname: Veenstra-VanderWeele
authors.forename: J
authors.initials: J
authors.lastname: Samuels
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
authors.forename: J T
authors.initials: JT
authors.lastname: McCracken
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: A J
authors.initials: AJ
authors.lastname: Fyer
authors.forename: S L
authors.initials: SL
authors.lastname: Rauch
authors.forename: M A
authors.initials: MA
authors.lastname: Riddle
authors.forename: M A
authors.initials: MA
authors.lastname: Grados
authors.forename: O J
authors.initials: OJ
authors.lastname: Bienvenu
authors.forename: B
authors.initials: B
authors.lastname: Cullen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Shugart
authors.forename: J
authors.initials: J
authors.lastname: Piacentini
authors.forename: S
authors.initials: S
authors.lastname: Rasmussen
authors.forename: G
authors.initials: G
authors.lastname: Nestadt
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
authors.forename: M A
authors.initials: MA
authors.lastname: Jenike
authors.forename: E H
authors.initials: EH
authors.lastname: Cook
authors.forename: D L
authors.initials: DL
authors.lastname: Pauls
authors.forename: G L
authors.initials: GL
authors.lastname: Hanna
authors.forename: C A
authors.initials: CA
authors.lastname: Mathews
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000737:chemistry / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D027322:Amino Acid Transport System X-AG; D005819:Genetic Markers