title: Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.
abstract: Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research.
authors.affiliation: Department of Psychology, Northwestern University.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vrshek-Schallhorn
authors.affiliation: Department of Psychology, Williams College.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Stroud
authors.affiliation: Department of Psychology, Northwestern University.
authors.forename: Susan
authors.initials: S
authors.lastname: Mineka
authors.affiliation: Department of Psychology, Northwestern University.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Zinbarg
authors.affiliation: School of Education and Social Policy and Cells to Society Center, Institute for Policy Research, Northwestern University.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Adam
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Redei
authors.affiliation: Department of Psychology, University of California-Los Angeles.
authors.forename: Constance
authors.initials: C
authors.lastname: Hammen
authors.affiliation: Department of Psychology, University of California-Los Angeles.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Craske
mesh_terms: D000293:Adolescent; D000483:Alleles; D003865:Major Depressive Disorder / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008137:Longitudinal Studies; D008297:Male; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide; D011985:Receptors, Serotonin / Q000235:genetics*; D012307:Risk Factors; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D011985:Receptors, Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase