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Genetic variation in 5HTTLPR is associated with emotional resilience.

ABSTRACT: Emotional resilience can be defined as the ability to maintain healthy and stable levels of psychological functioning in the wake of stress and trauma. Although genes that contribute to psychopathology (often in interaction with environmental stressors) are being detected with increasing consistency, genes that influence resilience to stress have been less studied. In this study, 423 undergraduate college students completed a psychometrically sound 10-item self-report measure of resilience (CDRISC-10) and provided blood for DNA. Linear and logistic regression analyses were used to model relationships between the serotonin transporter promoter polymorphism (5HTTLPR) and CDRISC-10 scores and categories, respectively. CDRISC-10 scores were normally distributed (mean 26.17, SD 5.88 [range 5-40]). In models adjusting for ancestry proportion scores (to mitigate confounding by population stratification) and other covariates, each copy of the "s" allele of 5HTTLPR was associated with approximately 1-point lower CDRISC-10 score. Each copy of the "s" allele was associated with increased (adjusted OR = 1.53, 95% CI 1.06-2.21, P = 0.024) odds of being in the low resilient category (>1 SD below the mean), compared to being homozygous for the "l" allele. These findings suggest that variation in 5HTTLPR is associated with individual differences in emotional resilience, defined as an individual's ability to withstand and bounce back from stress. This relationship may explain the frequently observed interaction between 5HTTLPR and life stressors in predicting adverse mental health outcomes (e.g., depressive symptoms). Replication is needed, in concert with identification of other genes that influence emotional resilience and related phenotypes.

SUBMITTER: Stein MB

PROVIDER: S-EPMC2885845 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Genetic variation in 5HTTLPR is associated with emotional resilience.

Stein Murray B MB Campbell-Sills Laura L Gelernter Joel J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20091001 7

Emotional resilience can be defined as the ability to maintain healthy and stable levels of psychological functioning in the wake of stress and trauma. Although genes that contribute to psychopathology (often in interaction with environmental stressors) are being detected with increasing consistency, genes that influence resilience to stress have been less studied. In this study, 423 undergraduate college students completed a psychometrically sound 10-item self-report measure of resilience (CDRI ...[more]

PMID: 19152387

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Project description:Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run across all participants and repeated restricting the sample to individuals with unimpaired cognition to identify variants at the earliest stages of disease. As expected, all resilience metrics were genetically correlated with cognitive performance and education attainment traits (P-values < 2.5 × 10-20), and we observed novel correlations with neuropsychiatric conditions (P-values < 7.9 × 10-4). Notably, neither resilience metric was genetically correlated with clinical Alzheimer's disease (P-values > 0.42) nor associated with APOE (P-values > 0.13). In single variant analyses, we observed a genome-wide significant locus among participants with unimpaired cognition on chromosome 18 upstream of ATP8B1 (index single nucleotide polymorphism rs2571244, minor allele frequency = 0.08, P = 2.3 × 10-8). The top variant at this locus (rs2571244) was significantly associated with methylation in prefrontal cortex tissue at multiple CpG sites, including one just upstream of ATPB81 (cg19596477; P = 2 × 10-13). Overall, this comprehensive genetic analysis of resilience implicates a putative role of vascular risk, metabolism, and mental health in protection from the cognitive consequences of neuropathology, while also providing evidence for a novel resilience gene along the bile acid metabolism pathway. Furthermore, the genetic architecture of resilience appears to be distinct from that of clinical Alzheimer's disease, suggesting that a shift in focus to molecular contributors to resilience may identify novel pathways for therapeutic targets.

Dataset Information

Genetic variation in 5HTTLPR is associated with emotional resilience.

Publications

Genetic variation in 5HTTLPR is associated with emotional resilience.

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