Discrimination and anxiety: Using multiple polygenic scores to control for genetic liability

Adolfo G. Cuevas, Frank D. Mann, David R. Williams, Robert F. Krueger

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8 Scopus citations


An established body of research indicates that discrimination is associated with increased symptoms of anxiety and negative affect. However, the association cannot be interpreted unambiguously as an exposure effect because a common set of genetic factors can simultaneously contribute to increased liability for symptoms of anxiety, negative affect, and the perception of discrimination. The present study elucidates the association between discrimination and anxiety/negative affect by implementing strict genetic controls in a large sample of adults. We used data from the biomarker project of the Study of Midlife Development in the United States (MIDUS), a national probability sample of noninstitutionalized, English-speaking respondents aged 25 to 74 y. Participants who consented to provide genetic data were biologically unrelated and of European ancestry as determined by genotype principal components analysis (n = 1,146). A single structural regression model was fit to the data with three measures of discrimination specified to load onto a latent factor and six measures of anxiety and negative affect specified to load onto a second latent factor. After accounting for potential genetic confounds—polygenic scores for anxiety, depression, and neuroticism and the first five genetic principal components—greater discrimination was associated with greater anxiety/negative affect (β = 0.53, SE = 0.04, P < 0.001). Findings suggest that measures of perceived discrimination should be considered environmental risk factors for anxiety/negative affect rather than indices of genetic liability for anxiety, depression, or neuroticism. Clinical interventions and prevention measures should focus on ways to mitigate the impact of discrimination to improve mental health at the population level.

Original languageEnglish (US)
Article numbere2017224118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 5 2021

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. The MIDUS study is supported by the John D. and Catherine T. MacArthur Foundation Research Network, National Institute on Aging (P01-AG020166), and the National Institute on Aging (U19-AG051426). Biomarker data collection was further supported by the National Institute of Health National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Science Award (CTSA) program as follows: UL1TR001409 (Georgetown), UL1TR001881 (UCLA), and 1UL1RR025011 (UW). The development of the manuscript was partially supported by Cancer Disparities Research Network/Geographic Management Program (GMaP) Region 4 funded by 3 P30 CA006927-52S2 and by the Clinical & Translational Science Institute Mentored Career Development Award (KL2 TR002545).

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.


  • Anxiety
  • Discrimination
  • Internalizing
  • Negative affect
  • Polygenic scores


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