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Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

ABSTRACT: Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology.

SUBMITTER: Venables NC

PROVIDER: S-EPMC5364073 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

Venables Noah C NC Hicks Brian M BM Yancey James R JR Kramer Mark D MD Nelson Lindsay D LD Strickland Casey M CM Krueger Robert F RF Iacono William G WG Patrick Christopher J CJ

International journal of psychophysiology : official journal of the International Organization of Psychophysiology 20160923

Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addres ...[more]

PMID: 27671504

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Project description:ObjectiveMental disorders are heritable and polygenic, and genome-wide genetic correlations (rg) have indicated widespread shared genetic risk across multiple disorders and related traits, mirroring their overlapping clinical characteristics. However, rg may underestimate the shared genetic underpinnings of mental disorders and related traits because it does not differentiate mixtures of concordant and discordant genetic effects from an absence of genetic overlap. Using novel statistical genetics tools, the authors aimed to evaluate the genetic overlap between mental disorders and related traits when accounting for mixed effect directions.MethodsThe authors applied the bivariate causal mixture model (MiXeR) to summary statistics for four mental disorders, four related mental traits, and height from genome-wide association studies (Ns ranged from 53,293 to 766,345). MiXeR estimated the number of "causal" variants for a given trait ("polygenicity"), the number of variants shared between traits, and the genetic correlation of shared variants (rgs). Local rg was investigated using LAVA.ResultsAmong mental disorders, ADHD was the least polygenic (5.6K "causal" variants), followed by bipolar disorder (8.6K), schizophrenia (9.6K), and depression (14.5K). Most variants were shared across mental disorders (4.4K-9.3K) and between mental disorders and related traits (5.2K-12.8K), but with disorder-specific variations in rg and rgs. Overlap with height was small (0.7K-1.1K). MiXeR estimates correlated with LAVA local rg (r=0.88, p<0.001).ConclusionsThere is extensive genetic overlap across mental disorders and related traits, with mixed effect directions and few disorder-specific variants. This suggests that genetic risk for mental disorders is predominantly differentiated by divergent effect distributions of pleiotropic genetic variants rather than disorder-specific variants. This represents a conceptual advance in our understanding of the landscape of shared genetic architecture across mental disorders, which may inform genetic discovery, biological characterization, nosology, and genetic prediction.

Dataset Information

Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

Publications

Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

Similar Datasets

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