title: Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts.
abstract: Some evidence suggests that genetic polymorphisms in oxytocin pathway genes influence various social behaviors, but findings thus far have been mixed. Many studies have been based in small samples and there is possibility of publication bias. Using data from 2 large U.S. prospective cohorts with over 11,000 individuals, we investigated 88 SNPs in OXTR, AVPR1A, and CD38, in relation to social integration (measured as social connectedness in both binary and continuous forms and being continuously married). After correction for multiple testing only one SNP in CD38 (rs12644506) was significantly associated with social integration and that SNP predicted when using a dichotomized indicator of social connectedness (adjusted p=0.02), but not a continuous measure of social connectedness or the continuously married outcome. A significant gender-heterogeneous effect was identified in one OXTR SNP on dichotomized social connectedness; specifically, rs4686302 T allele was nominally associated with social connectedness in men, whereas the association direction was opposite in women (adjusted gender heterogeneity p=0.02). Furthermore, the rs53576 A allele was significantly associated with social connectedness only in women, and the effect magnitude was stronger in a dominant genetic model (adjusted p=0.003). In summary, our findings suggested that common genetic variants of OXTR, CD38, and AVPR1A are not associated with social integration as measured in this study using the simplified Berkman-Syme Social Network Index, but these findings and other work hint that effects may be modified by gender or other social experiences. Further work considering genetic pathways in relation to social integration may be more fruitful if these additional factors can be more comprehensively evaluated.
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States. Electronic address: scchang@hsph.harvard.edu.
authors.forename: Shun-Chiao
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States; Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, United States.
authors.forename: M Maria
authors.initials: MM
authors.lastname: Glymour
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Marissa
authors.initials: M
authors.lastname: Rewak
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Walter
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States.
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawachi
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tchetgen Tchetgen
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kubzansky
mesh_terms: D000483:Alleles; D017252:CD3 Complex / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000235:genetics*; D012737:Sex Factors; D012919:Social Behavior; D012934:Social Isolation
chemical_list: D017252:CD3 Complex; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin
keywords: AVPR1A; CD38; Candidate gene; OXTR; Sex-specific; Social integration