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An atlas of genetic correlations across human diseases and traits

Nature Genetics volume 47, pages 1236–1241 (2015)Cite this article

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Abstract

Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique—cross-trait LD Score regression—for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment.

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Figure 1: Replication of psychiatric cross-disorder results.
Figure 2: Genetic correlations among 24 traits analyzed by genome-wide association.

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Acknowledgements

We would like to thank P. Sullivan, C. Bulik, S. Caldwell, C. Arabica and O. Andreassen for helpful comments. This work was supported by US National Institutes of Health (NIH) grants R01 MH101244 (A.L.P.), R01 HG006399 (N.P.), 1R01 MH101244-02 (B.M.N.), 5U01 MH094432-03 (B.M.N.) and R03 CA173785 (H.K.F.) and by the Fannie and John Hertz Foundation (H.K.F.). Data on anorexia nervosa were obtained by funding from the Wellcome Trust Case Control Consortium 3 project titled “A Genome-Wide Association Study of Anorexia Nervosa” (WT088827/Z/09). Data on glycemic traits were contributed by MAGIC investigators and were downloaded from http://www.magicinvestigators.org/. Data on coronary artery disease and myocardial infarction were contributed by CARDIoGRAMplusC4D investigators and were downloaded from http://www.cardiogramplusc4d.org/.

We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in the analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients and their families. The work with iSelect chips was funded by the French National Foundation on Alzheimer's Disease and Related Disorders. EADI was supported by a LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant, INSERM, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council, UK (grant 503480), Alzheimer's Research UK (grant 503176), the Wellcome Trust (grant 082604/2/07/Z) and the German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grants 01GI0102 and 01GI0711, 01GI0420. CHARGE was partly supported by US NIH/National Institute on Aging grants R01 AG033193 and AG081220 and AGES contract N01-AG-12100, National Heart, Lung, and Blood Institute (NHLBI) grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by US NIH/National Institute on Aging grants U01 AG032984, U24 AG021886 and U01 AG016976 and Alzheimer's Association grant ADGC-10-196728.

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Author notes

  1. Brendan Bulik-Sullivan and Hilary K Finucane: These authors contributed equally to this work.

  2. Alkes L Price and Benjamin M Neale: These authors jointly supervised this work.

Authors and Affiliations

  1. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

    Brendan Bulik-Sullivan, Verneri Anttila, Po-Ru Loh, Laramie Duncan, Nick Patterson, Elise B Robinson, Mark J Daly, Alkes L Price & Benjamin M Neale

  2. Stanley Center for Psychiatric Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

    Brendan Bulik-Sullivan, Verneri Anttila, Laramie Duncan, Elise B Robinson, Mark J Daly & Benjamin M Neale

  3. Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Brendan Bulik-Sullivan, Verneri Anttila, Laramie Duncan, Elise B Robinson, Mark J Daly & Benjamin M Neale

  4. Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Hilary K Finucane

  5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Alexander Gusev, Po-Ru Loh & Alkes L Price

  6. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Alexander Gusev & Alkes L Price

  7. Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK

    Felix R Day & John R B Perry

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  1. Brendan Bulik-Sullivan
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Consortia

ReproGen Consortium

Psychiatric Genomics Consortium

Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3

Contributions

M.J.D., A.G., P.-R.L., L.D., N.P., B.M.N. and A.L.P. provided reagents. E.B.R., V.A., J.R.B.P. and F.R.D. aided in the interpretation of results. J.R.B.P. and F.R.D. provided data on age at menarche. B.B.-S. and H.K.F. are responsible for the remainder. All authors revised and approved the final manuscript.

Corresponding authors

Correspondence to Brendan Bulik-Sullivan, Hilary K Finucane, Alkes L Price or Benjamin M Neale.

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The authors declare no competing financial interests.

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A full list of members and affiliations appears in the Supplementary Note.

A full list of members and affiliations appears in the Supplementary Note.

A full list of members and affiliations appears in the Supplementary Note.

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Supplementary Figures 1–6, Supplementary Tables 1–3 and Supplementary Note. (PDF 1308 kb)

Supplementary Table 4

Table of genetic correlations. (CSV 63 kb)

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Bulik-Sullivan, B., Finucane, H., Anttila, V. et al. An atlas of genetic correlations across human diseases and traits. Nat Genet 47, 1236–1241 (2015). https://doi.org/10.1038/ng.3406

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