Estimating the heritability of reporting stressful life events captured by common genetic variants

Power, Robert A.; Wingenbach, Tanja S. H.; Cohen‐Woods, Sarah; Uher, Rudolf; Ng, Mandy; Butler, Amy W.; Ising, Marcus; Craddock, Nick; Owen, Michael John; Korszun, Ania; Jones, Lisa; Jones, Ian; Gill, Michael; Rice, John P.; Maier, Wolfgang; Zobel, Astrid; Mors, Ole; Placentino, Anna; Rietschel, Marcella; Holsboer, Florian; Binder, Elisabeth B.; Keers, Robert; Tozzi, Federica; Muglia, Pierandrea; Breen, Gerome; Craig, Ian W.; Müller‐Myhsok, Bertram; Kennedy, James L.; Strauss, John S.; Vincent, John B.; Lewis, Cathryn M.; Farmer, Anne; McGuffin, Peter

doi:10.1017/s0033291712002589

Cited by 47 publications

(82 citation statements)

References 30 publications

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“…Finally, studies using methods that are not subject to the limitations of the twin design (e.g. genome-wide complex trait analysis; adoption studies), have found heritability estimates for depression (Lubke et al, 2012; Sullivan et al, 2000) and life events (Bemmels et al, 2008; Power et al, 2012) that are consistent with the estimates in our sample.…”

Section: Discussionsupporting

confidence: 83%

A Behavior Genetic Analysis of Pleasant Events, Depressive Symptoms, and Their Covariation

Whisman

Johnson

Rhee

2014

Clinical Psychological Science

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Although pleasant events figure prominently in behavioral models of depression, little is known regarding characteristics that may predispose people to engage in pleasant events and derive pleasure from these events. The present study was conducted to evaluate genetic and environmental influences on the experience of pleasant events, depressive symptoms, and their covariation in a sample of 148 twin pairs. A multivariate twin modeling approach was used to examine the genetic and environmental covariance of pleasant events and depressive symptoms. Results indicated that the experience of pleasant events was moderately heritable and that the same genetic factors influence both the experience of pleasant events and depressive symptoms. These findings suggest that genetic factors may give rise to dispositional tendencies to experience both pleasant events and depression.

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Section: Discussionsupporting

confidence: 83%

A Behavior Genetic Analysis of Pleasant Events, Depressive Symptoms, and Their Covariation

Whisman

Johnson

Rhee

2014

Clinical Psychological Science

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“…There is no question that both genes and environment influence risk for depression, and recent evidence suggests that exposure to stressful life events is, itself, heritable (Power et al, 2013). However, G × E studies ask the more specific question of whether the joint effect of genetic variation and environmental risk factors is significantly different from the product of their individual effects.…”

Section: Gene-environment Interactionmentioning

confidence: 99%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

349

243

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Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

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“…These studies have shown that variation in individuals' social deprivation, household income, stressful life events, and family socioeconomic status partially reflects individuals' differences across genome-wide common genetic variants measured on SNP arrays (38)(39)(40)(41)(42)(43)(44). There have also been a few reports of extending SNP heritability analysis to estimate genetic correlations between environmental measures and measures of children's developmental outcomes (38)(39)(40).…”

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confidence: 99%

Widespread covariation of early environmental exposures and trait-associated polygenic variation

Krapohl

Hannigan

Pingault

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between traitassociated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring traitassociated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R 2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R 2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R 2 = 0.008; P = 5e-13), parental smacking (R 2 = 0.01; P = 4e-15), household income (R 2 = 0.032; P = 1e-22), watching television (R 2 = 0.034; P = 5e-47), and maternal education (R 2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.environmental risk | polygenic scores | gene-environment correlation | human complex traits | prediction

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Estimating the heritability of reporting stressful life events captured by common genetic variants

Abstract: These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.

Cited by 47 publications

References 30 publications

A Behavior Genetic Analysis of Pleasant Events, Depressive Symptoms, and Their Covariation

A Behavior Genetic Analysis of Pleasant Events, Depressive Symptoms, and Their Covariation

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Widespread covariation of early environmental exposures and trait-associated polygenic variation

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