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Genetic correlates of socio-economic status influence the pattern of shared heritability across mental health traits

Abstract

Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic factors across mental health traits. However, mental health is also genetically correlated with socio-economic status (SES), and it is therefore important to investigate and disentangle the genetic relationship between mental health and SES. We used summary statistics from large genome-wide association studies (average N ~ 160,000) to estimate the genetic overlap across nine psychiatric disorders and seven substance use traits and explored the genetic influence of three different indicators of SES. Using genomic structural equation modelling, we show significant changes in patterns of genetic correlations after partialling out SES-associated genetic variation. Our approach allows the separation of disease-specific genetic variation and genetic variation shared with SES, thereby improving our understanding of the genetic architecture of mental health.

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Fig. 1: Estimated genetic correlation (solid bidirectional arrow) between two traits of interest 1 and 2 (T1, T2).
Fig. 2
Fig. 3
Fig. 4: Genetic correlations before and after partialling out the SES factor.
Fig. 5: SNP-based genetic correlations between the mental health traits.

Data availability

This research was conducted using data downloadable from: https://www.med.unc.edu/pgc/download-results/, https://www.ru.nl/bsi/research/group-pages/substance-use-addiction-food-saf/vm-saf/genetics/international-cannabis-consortium-icc/, https://www.thessgac.org/data and https://www.ccace.ed.ac.uk/node/335. Summary statistics for the phenotypes ‘alcohol consumption frequency’ and ‘alcohol consumption quantity’ are available from the corresponding authors on request.

Code availability

Code used for the analyses is available on https://github.com/MareesAT/Genetic-correlates-of-socio-economic-status-influence-the-pattern-of-shared-heritability-across-ment.

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Acknowledgements

A.A., A.T.M. and K.J.H.V. are supported by the Foundation Volksbond Rotterdam. A.T.M. and T.J.G. are supported by the Netherlands Organization for Research (NWO) Vidi grant 0.16.Vidi.185.044. M.G.N. is supported by ZonMW grants 849200011 and 531003014 from the Netherlands Organisation for Health Research and Development. This research was supported by the National Institute on Aging, under grants RF1055654 and R56AG058726.

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Contributions

A.T.M., D.J.A.S. and A.A. performed the analyses. M.G.N. designed the methodology. K.J.H.V. and E.M.D. supervised the project. A.T.M., D.J.A.S., A.A., K.J.H.V. and E.M.D. wrote the manuscript. D.D., M.G.N., T.J.G. and W.v.d.B. provided feedback and edited the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Andries T. Marees or Eske M. Derks.

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The authors declare no competing interests.

Additional information

Peer review information Nature Human Behaviour thanks Shuquan Rao, Rebecca Richmond and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor(s): Charlotte Payne.

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Extended data

Extended Data Fig. 1

Genetic correlations between SES indicators and 9 psychiatric disorders and 7 substance use traits as computed with LDSC (error bars show ± 2×SE).

Extended Data Fig. 2

Genetic variance explained by SNPs before (SNP-based heritability) and after removing genetic effects overlapping with the SES indicators (error bars show ± 2×SE).

Extended Data Fig. 3 Genetic correlations before and after partialling out educational attainment (EA).

Significant genetic correlations are indicated with red circles and significant changes in genetic correlations after partialling out EA are indicated in red letters.

Extended Data Fig. 4 Genetic correlations before and after partialling out household income (HI).

Significant genetic correlations are indicated with red circles and significant changes in genetic correlations after partialling out HI are indicated in red letters.

Extended Data Fig. 5 Genetic correlations before and after partialling out Townsend index (TI).

Significant genetic correlations are indicated with red circles and significant changes in genetic correlations after partialling out HI are indicated in red letters.

Extended Data Fig. 6 Genetic correlations before (x-axis) and after (y-axis) partialling out SES. Each dot represents one of the mental health or substance use traits.

Significant changes in genetic correlations after partialling out SES are indicated as red dots. The four correlations on top of the Figures are the Pearson correlations between the genetic correlations before and after partialling out the SES factors.

Extended Data Fig. 7 The genetic correlations before (lower diagonal, in black font) and after (upper diagonal, in green font) partialling out latent genetic SES factor variance.

Coloured squares indicate significant genetic correlations (FDR corrected, see methods).

Extended Data Fig. 8 The genetic correlations before (lower diagonal in black type) and after (upper diagonal in green type) partialling out genetic variance of educational attainment.

Coloured squares indicate significant genetic correlations (FDR corrected, see methods).

Extended Data Fig. 9 The genetic correlations before (lower diagonal in black type) and after (upper diagonal in green type) partialling out genetic variance of household income.

Coloured squares indicate significant genetic correlations (FDR corrected, see methods).

Extended Data Fig. 10 The genetic correlations before (lower diagonal in black type) and after (upper diagonal in green type) partialling out genetic variance of the Townsend index.

Coloured squares indicate significant genetic correlations (FDR corrected, see methods).

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Marees, A.T., Smit, D.J.A., Abdellaoui, A. et al. Genetic correlates of socio-economic status influence the pattern of shared heritability across mental health traits. Nat Hum Behav (2021). https://doi.org/10.1038/s41562-021-01053-4

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