• DOI:10.1002/ajmg.b.32137
• Corpus ID: 20929721

Meta‐analysis of association between obsessive‐compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1

@article{Stewart2013MetaanalysisOA,
  title={Meta‐analysis of association between obsessive‐compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1},
  author={S. Evelyn Stewart and C Mayerfeld and Paul D. Arnold and Jacquelyn Crane and Colm O'Dushlaine and Jesen A. Fagerness and D. Yu and J M Scharf and Eh Chan and F Kassam and Pablo R Moya and Jens R. Wendland and Richard Delorme and Margaret Anne Richter and James L. Kennedy and Jeremy Veenstra-VanderWeele and J. F. Samuels and Benjamin D. Greenberg and James T. McCracken and James A. Knowles and Abby J Fyer and Scott L. Rauch and Mark A. Riddle and Marco A Grados and O. Joseph Bienvenu and Bernadette A. Cullen and Ying Wang and Yin Yao Shugart and John Piacentini and Steven A. Rasmussen and Gerald Nestadt and Dennis L. Murphy and Michael A. Jenike and Edwin H. Cook and David L. Pauls and Gregory L. Hanna and Carol A. Mathews},
  journal={American Journal of Medical Genetics Part B: Neuropsychiatric Genetics},
  year={2013},
  volume={162}
}

• S. Stewart, C. Mayerfeld, +34 authors C. Mathews
• Published 1 June 2013
• Medicine
• American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

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. © 2013 Wiley Periodicals, Inc.