Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships.
ABSTRACT There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34,371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller--but statistically powerful--sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.
Full-textDOI: · Available from: Ian W Craig, Jun 18, 2015
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ABSTRACT: Although there is growing evidence of links between the cortisol stress response and personality, the nature of the relationships and the underlying mechanisms require further clarification. The purpose of this study was to examine associations between personality traits and cortisol responses to stress using the Revised NEO Personality Inventory five-factor model of personality. In total, 68 healthy adults, aged 18-30 years, completed the personality assessment and underwent a laboratory psychological stress test that consisted of a 5 min speech and 5-min of mental arithmetic. Findings showed that in the sample as a whole, less Openness was associated with lower cortisol responses to the challenge. Cortisol responses also corresponded to certain personality dimensions in a gender-specific manner. Blunted cortisol responses were associated with higher Neuroticism in women and with lower Extraversion in men. These findings suggest that personality traits that have been traditionally associated with greater psychopathology were also associated with blunted HPA axis responses to stress.Neuropsychopharmacology 08/2006; 31(7):1583-91. DOI:10.1038/sj.npp.1301012 · 7.83 Impact Factor
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ABSTRACT: Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD. Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998-2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972-1973. In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1.00 in females and +0.74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0.59 in males and +0.36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD. Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.Psychological Medicine 04/2007; 37(3):453-62. DOI:10.1017/S0033291706009135 · 5.43 Impact Factor