Lack of Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Alexithymia: Evidence from Patients with Obsessive-Compulsive Disorder

<div><p>Oxytocin receptor gene single nucleotide polymorphisms have been associated with structural and functional alterations in brain regions, which involve social-emotional processing. Therefore, oxytocin receptor gene polymorphisms may contribute to individual differences in alexithymia, which is considered to be a dysfunction of emotional processing. The aim of this study was to evaluate the association between oxytocin receptor gene single nucleotide polymorphisms or haplotypes and alexithymia in patients with obsessive-compulsive disorder. We recruited 355 patients with obsessive-compulsive disorder (234 men, 121 women). Alexithymia was measured by using the Toronto Alexithymia Scale. We performed single-marker and haplotype association analyses with eight single nucleotide polymorphisms (rs237885, rs237887, rs2268490, rs4686301, rs2254298, rs13316193, rs53576, and rs2268498) in the oxytocin receptor gene. There were no significant associations between any of the eight single nucleotide polymorphism of the oxytocin receptor gene and alexithymia. In addition, a six-locus haplotype block (rs237885-rs237887-rs2268490-rs4686301-rs2254298-rs13316193) was not significantly associated with alexithymia. These findings suggest that genetic variations in the oxytocin receptor gene may not explain a significant part of alexithymia in patients with obsessive-compulsive disorder.</p></div

Linkage disequilibrium (LD) structure of the single-nucleotide polymorphisms and a haplotype block analyzed in the current study (Block1:SNP1-SNP6).

<p>Linkage disequilibrium (LD) structure of the single-nucleotide polymorphisms and a haplotype block analyzed in the current study (Block1:SNP1-SNP6).</p

Selection of OXTR single-nucleotide polymorphism (SNP).

<p>Circle denote SNPs significantly associated with prosocial behavior in single-marker analyses of previous studies, with asterisks representing SNPs included the current association study.</p

Analysis configurations and number of genetic variants incorporated.

Analysis configurations and number of genetic variants incorporated.</p

Power curves for RITSS1, RITSS2, GESAT, and GAMsv over increasing signal density <i>p</i>_<i>XE</i>.

Significance level α = 0.005, μXE = 0.1, and results based on 1,000 replicates. Power was simulated for pXE = 0.05, 0.1, 0.2, 0.3, 0.4, 0.5.</p

Power curves for RITSS1, RITSS2, GESAT, and GAMsv over increasing signal density <i>p</i>_<i>XE</i>.

Significance level α = 0.005, μXE = 0.05, and results based on 1,000 replicates. Power was simulated for pXE = 0.05, 0.1, 0.2, 0.3, 0.4, 0.5.</p

Additional information regarding genetic variants tested in the UK Biobank analysis.

These tables contain all genetic variants as well as the m4/m3 information for the sex-interaction analysis in the UK Biobank. (XLSX)</p

Density plots for standardized residuals for all four traits in the analysis.

FEV1: forced expiratory volume in 1 second, FVC: forced vital capacity. (TIF)</p

Type 1 error: Quantile-quantile-plots for RITSS1, RITSS2, GESAT, and GAMsv for scenarios 1–5 with SELECT:yes.

All results based on 10,000 replicates. P-values with p−10 were set to p = 10−10. SELECT:yes refers to the scenario where the simulated genetic variants are selected into the analysis based on marginal association p-values.</p

Type 1 error: Quantile-quantile-plots for RITSS1, RITSS2, GESAT, and GAMsv for scenarios 1–5 with SELECT:no.

All results based on 10,000 replicates. P-values with p−10 were set to p = 10−10. SELECT:no refers to the scenario where all simulated genetic variants are included in the analysis.</p