Genetic correlations of polygenic disease traits: from theory to practice

doi:10.1038/s41576-019-0137-z

Review

. 2019 Oct;20(10):567-581.

doi: 10.1038/s41576-019-0137-z.

Genetic correlations of polygenic disease traits: from theory to practice

Wouter van Rheenen¹, Wouter J Peyrot², Andrew J Schork³, S Hong Lee⁴, Naomi R Wray^{5

6}

Affiliations

¹ Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands. w.vanrheenen-2@umcutrecht.nl.
² Department of Psychiatry, Amsterdam UMC, VU University Medical Center, Amsterdam, Netherlands.
³ Institute for Biological Psychiatry, Mental Health Services Snct. Hans, Roskilde, Denmark.
⁴ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.
⁵ Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.
⁶ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.

PMID: 31171865
DOI: 10.1038/s41576-019-0137-z

Review

Genetic correlations of polygenic disease traits: from theory to practice

Wouter van Rheenen et al. Nat Rev Genet. 2019 Oct.

. 2019 Oct;20(10):567-581.

doi: 10.1038/s41576-019-0137-z.

Authors

Wouter van Rheenen¹, Wouter J Peyrot², Andrew J Schork³, S Hong Lee⁴, Naomi R Wray^{5

6}

Affiliations

¹ Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands. w.vanrheenen-2@umcutrecht.nl.
² Department of Psychiatry, Amsterdam UMC, VU University Medical Center, Amsterdam, Netherlands.
³ Institute for Biological Psychiatry, Mental Health Services Snct. Hans, Roskilde, Denmark.
⁴ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.
⁵ Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.
⁶ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.

PMID: 31171865
DOI: 10.1038/s41576-019-0137-z

Abstract

The genetic correlation describes the genetic relationship between two traits and can contribute to a better understanding of the shared biological pathways and/or the causality relationships between them. The rarity of large family cohorts with recorded instances of two traits, particularly disease traits, has made it difficult to estimate genetic correlations using traditional epidemiological approaches. However, advances in genomic methodologies, such as genome-wide association studies, and widespread sharing of data now allow genetic correlations to be estimated for virtually any trait pair. Here, we review the definition, estimation, interpretation and uses of genetic correlations, with a focus on applications to human disease.

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References

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[1] Polderman, T. J. C. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015). - PubMed

[2] Polderman, T. J. C. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015). - PubMed

[3] Craddock, N. & Owen, M. J. The beginning of the end for the Kraepelinian dichotomy. Br. J. Psychiatry 186, 364–366 (2005). - PubMed

[4] Craddock, N. & Owen, M. J. The beginning of the end for the Kraepelinian dichotomy. Br. J. Psychiatry 186, 364–366 (2005). - PubMed

[5] Maret-Ouda, J., Tao, W., Wahlin, K. & Lagergren, J. Nordic registry-based cohort studies: possibilities and pitfalls when combining Nordic registry data. Scand. J. Public Health 45 (Suppl. 17), 14–19 (2017). - PubMed

[6] Maret-Ouda, J., Tao, W., Wahlin, K. & Lagergren, J. Nordic registry-based cohort studies: possibilities and pitfalls when combining Nordic registry data. Scand. J. Public Health 45 (Suppl. 17), 14–19 (2017). - PubMed

[7] Lichtenstein, P. et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239 (2009). This work reports a population-scale data set for estimation of genetic correlation between diseases based on family data. - PubMed

[8] Lichtenstein, P. et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239 (2009). This work reports a population-scale data set for estimation of genetic correlation between diseases based on family data. - PubMed

[9] Stearns, F. W. One hundred years of pleiotropy: a retrospective. Genetics 186, 767–773 (2010). - PubMed - PMC

[10] Stearns, F. W. One hundred years of pleiotropy: a retrospective. Genetics 186, 767–773 (2010). - PubMed - PMC

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Genetic correlations of polygenic disease traits: from theory to practice

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Genetic correlations of polygenic disease traits: from theory to practice

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