The association of sex, age and FKBP5 genotype with common somatic symptoms: A replication study in the lifelines cohort study

Abstract

Objective: Our aim was to replicate a recent study that reported an association between the rs9470080 CC-genotype and common somatic symptoms in women, but not in men. Additionally, we quantified the genetic contribution to phenotypic variation in common somatic symptom levels.

Methods: We used data from the Lifelines Cohort Study, including 28,299 participants (60.0% female; 44.2% CC-genotype; mean age 42.9 (14.2) years). Common somatic symptoms were measured with the SCL-90 SOM subscale. To assess the association between the rs9470080 genotype and SCL-90 SOM scores we applied similar analyses as the original study, including independent t-tests, two-way ANOVAs and a mixed ANOVA. To estimate the proportion of phenotypic variance in SCL-90 SOM scores explained by single nucleotide polymorphisms (SNPs), we used a genomic-relatedness-based restricted maximum-likelihood method.

Results: We could not replicate the original study's findings. We found no association between the rs9470080 genotype and common somatic symptom levels in either female or male participants (F(1, 8775) = 1.07, p = 0.30 and F(1,13,903) = 0.01, p = 0.93, respectively). Genome-wide heritability analyses show that 12.1% (p = 2.1e-08) of the phenotypic variance in common somatic symptom levels in Lifelines can be explained by SNPs. The genetic contribution to common somatic symptom levels was higher in male participants (SNP-h² = 20.5%; p = 9.1e-08) than in female participants (SNP-h² = 12.0%, p = 2.8e-05).

Conclusion: Our findings of significant SNP-h² and the sex-specific differences herein, does warrant further sex-stratified research of individual genetic variants associated with common somatic symptoms. Preferably, further research should be performed within the analytic framework of a genome-wide association study.

Keywords: Common somatic symptoms; Replication; Sex differences.