Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder

Uzoezi Ozomaro, Guiqing Cai, Yuji Kajiwara, Seungtai Yoon, Vladimir Makarov, Richard Delorme, Catalina Betancur, Stephan Ruhrmann, Peter Falkai, Hans Jörgen Grabe, Wolfgang Maier, Michael Wagner, Leonhard Lennertz, Rainald Moessner, Dennis L. Murphy, Joseph D. Buxbaum, Stephan L Zuchner, Dorothy E. Grice

Research output: Contribution to journalArticle

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Abstract

Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and intrusive thoughts and ritualistic behaviors or mental acts that a person feels compelled to perform. Twin studies, family studies, and segregation analyses provide compelling evidence that OCD has a strong genetic component. The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum, specifically Tourette syndrome (TS) and trichotillomania (TTM). The objective of the current study was to evaluate rare genetic variation in SLITRK1 in risk for OCD and to functionally characterize associated coding variants. We sequenced SLITRK1 coding exons in 381 individuals with OCD as well as in 356 control samples and identified three novel variants in seven individuals. We found that the combined mutation load in OCD relative to controls was significant (p = 0.036). We identified a missense N400I change in an individual with OCD, which was not found in more than 1000 control samples (P<0.05). In addition, we showed the the N400I variant failed to enhance neurite outgrowth in primary neuronal cultures, in contrast to wildtype SLITRK1, which enhanced neurite outgrowth in this assay. These important functional differences in the N400I variant, as compared to the wildtype SLITRK1 sequence, may contribute to OCD and OC spectrum symptoms. A synonymous L63L change identified in an individual with OCD and an additional missense change, T418S, was found in four individuals with OCD and in one individual without an OCD spectrum disorder. Examination of additional samples will help assess the role of rare SLITRK1 variation in OCD and in related psychiatric illness.

Original languageEnglish
Article numbere70376
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 21 2013

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obsessive-compulsive disorder
Obsessive-Compulsive Disorder
Genes
neurites
Exons
Assays
trichotillomania
Trichotillomania
family studies
Tourette Syndrome
Twin Studies
sampling
exons
Psychiatry

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ozomaro, U., Cai, G., Kajiwara, Y., Yoon, S., Makarov, V., Delorme, R., ... Grice, D. E. (2013). Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder. PLoS One, 8(8), [e70376]. https://doi.org/10.1371/journal.pone.0070376

Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder. / Ozomaro, Uzoezi; Cai, Guiqing; Kajiwara, Yuji; Yoon, Seungtai; Makarov, Vladimir; Delorme, Richard; Betancur, Catalina; Ruhrmann, Stephan; Falkai, Peter; Grabe, Hans Jörgen; Maier, Wolfgang; Wagner, Michael; Lennertz, Leonhard; Moessner, Rainald; Murphy, Dennis L.; Buxbaum, Joseph D.; Zuchner, Stephan L; Grice, Dorothy E.

In: PLoS One, Vol. 8, No. 8, e70376, 21.08.2013.

Research output: Contribution to journalArticle

Ozomaro, U, Cai, G, Kajiwara, Y, Yoon, S, Makarov, V, Delorme, R, Betancur, C, Ruhrmann, S, Falkai, P, Grabe, HJ, Maier, W, Wagner, M, Lennertz, L, Moessner, R, Murphy, DL, Buxbaum, JD, Zuchner, SL & Grice, DE 2013, 'Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder', PLoS One, vol. 8, no. 8, e70376. https://doi.org/10.1371/journal.pone.0070376
Ozomaro U, Cai G, Kajiwara Y, Yoon S, Makarov V, Delorme R et al. Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder. PLoS One. 2013 Aug 21;8(8). e70376. https://doi.org/10.1371/journal.pone.0070376
Ozomaro, Uzoezi ; Cai, Guiqing ; Kajiwara, Yuji ; Yoon, Seungtai ; Makarov, Vladimir ; Delorme, Richard ; Betancur, Catalina ; Ruhrmann, Stephan ; Falkai, Peter ; Grabe, Hans Jörgen ; Maier, Wolfgang ; Wagner, Michael ; Lennertz, Leonhard ; Moessner, Rainald ; Murphy, Dennis L. ; Buxbaum, Joseph D. ; Zuchner, Stephan L ; Grice, Dorothy E. / Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder. In: PLoS One. 2013 ; Vol. 8, No. 8.
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