Abstract
ObjectiveOur 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. MethodsWe 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. ResultsWe 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). ConclusionOur 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.
Highlights
Sex is increasingly recognized as a pivotal concept in health research [1,2]
We found no significant difference in common somatic symptom levels between rs9470080 genotype groups in male or female participants
The two-way ANOVA showed that the main effect of female sex, adjusted for age groups, on SCL-90 SOM scores was statistically signif icant: F(1, 28,294) = 563.0, p < 0.001
Summary
Sex is increasingly recognized as a pivotal concept in health research [1,2]. In many diseases, including autoimmune disorders and cardio vascular disease, studies found sex differences in prevalence and pre sentation [3,4]. Sex differences in the prevalence and longevity of common somatic symptoms are thought to associate with biological attributes, such as differences between male and female anatomy, hormones and genes [7,8,9]. Gender, the psychosocial equivalent of biological sex encompassing the embodiment of different roles, behaviors, identities and relationships of men and women pre scribed by social norms, affects the prevalence of common somatic symptoms. Previous studies show that a sex-by-gender role interaction associates with common somatic symptoms [7,8]. This may point to ward a gene-by-environment (GxE) interaction associating with com mon somatic symptom levels
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