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Genetic risk for neuroticism predicts emotional health depending on childhood adversity

Published online by Cambridge University Press:  26 March 2018

Kelli Lehto ,
Ida Karlsson ,
Cecilia Lundholm  and
Nancy L. Pedersen
Kelli Lehto*
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden Department of Chronic Diseases, Institute for Health Development, Hiiu 42, 11619, Tallinn, Estonia
Ida Karlsson
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden
Cecilia Lundholm
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden
Nancy L. Pedersen
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden
*
Author for correspondence: Kelli Lehto, E-mail: [email protected]
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Abstract

Background

Existing evidence for gene × environment interaction (G × E) in neuroticism largely relies on candidate gene studies, although neuroticism is highly polygenic. This study aimed to investigate the long-term associations between polygenic risk scores for neuroticism (PRSN), objective childhood adversity and their interplay on emotional health aspects such as neuroticism itself, depressive symptoms, anxiety symptoms, loneliness and life satisfaction.

Methods

The sample consisted of reared-apart (TRA) and reared-together (TRT) middle- and old age twins (N = 699; median age at separation = 2). PRSN were created under nine p value cut-off thresholds (pT-s) and the pT with the highest degree of neuroticism variance explained was chosen for subsequent analyses. Linear regressions were used to assess the associations between PRSN, childhood adversity (being reared apart) and emotional health. G × E was further investigated using a discordant twin design.

Results

PRSN explained up to 1.7% (pT < 0.01) of phenotypic neuroticism in the total sample. Analyses across two separation groups revealed substantial heterogeneity in the variance explained by PRSN; 4.3% was explained in TRT, but almost no effect was observed in TRA. Similarly, PRSN explained 4% and 1.7% of the variance in depressive symptoms and loneliness, respectively, only in TRT. A significant G × E interaction was identified for depressive symptoms.

Conclusions

By taking advantage of a unique sample of adopted twins, we demonstrated the presence of G × E in neuroticism and emotional health using PRSN and childhood adversity. Our results may indicate that genome-wide association studies are detecting genetic main effects associated with neuroticism, but not those susceptible to early environmental influences.

Keywords

neuroticismdepressive symptomsanxiety symptomslonelinessself-rated healthpolygenic risk scoreschildhood adversitygene-environment interactiontwinsgenetic
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 2 , January 2019 , pp. 260 - 267
Copyright
Copyright © Cambridge University Press 2018 

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