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Leveraging population admixture to characterize the heritability of complex traits

Nature Genetics volume 46, pages 1356–1362 (2014)Cite this article

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Abstract

Despite recent progress on estimating the heritability explained by genotyped SNPs (h2g), a large gap between h2g and estimates of total narrow-sense heritability (h2) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h2 due to shared environment or epistasis. We estimate h2 from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h2γ). We show that h2γ = 2FSTCθ(1 − θ)h2, where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h2 estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h2g in these and other data but smaller than family-based estimates of h2.

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Figure 1: Relationships between genetic distance and phenotype for a trait with heritability of 80%.
Figure 2: Estimated heritability of height for each chromosome in the CARe data set.

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Acknowledgements

This research was supported by US National Institutes of Health grants R01 HG006399, R01 GM073059, 1K25HL121295-01A1 and R21 ES020754. The WHI program is funded by the National Heart, Lung, and Blood Institute, US National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C.

Author information

Author notes

  1. Hua Tang and Alkes L Price: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, University of California, San Francisco, San Francisco, California, USA.,

    Noah Zaitlen

  2. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.,

    Bogdan Pasaniuc

  3. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

    Sriram Sankararaman, Gaurav Bhatia, Alexander Gusev, Taylor Young, Arti Tandon, Samuela Pollack, Bjarni J Vilhjálmsson, Nick Patterson, David Reich & Alkes L Price

  4. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

    Sriram Sankararaman, Arti Tandon & David Reich

  5. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

    Gaurav Bhatia, Alexander Gusev, Samuela Pollack, Bjarni J Vilhjálmsson & Alkes L Price

  6. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA

    Gaurav Bhatia, Alexander Gusev, Samuela Pollack, Bjarni J Vilhjálmsson & Alkes L Price

  7. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,

    Jianqi Zhang, Jing He, Sue A Ingles, Christopher Haiman & Daniel Stram

  8. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

    Themistocles L Assimes

  9. Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA

    Sonja I Berndt & Stephen Chanock

  10. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    William J Blot

  11. Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    William J Blot

  12. International Epidemiology Institute, Rockville, Maryland, USA

    William J Blot

  13. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA

    Nora Franceschini & Eric A Whitsel

  14. SWOG Statistical Center, Seattle, Washington, USA

    Phyllis G Goodman

  15. Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA

    Anselm J M Hennis & Barbara Nemesure

  16. Chronic Disease Research Centre, University of the West Indies, Bridgetown, Barbados

    Anselm J M Hennis

  17. Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados

    Anselm J M Hennis

  18. Ministry of Health, Bridgetown, Barbados

    Anselm J M Hennis

  19. Cancer Prevention Institute of California, Fremont, California, USA

    Ann Hsing

  20. Division of Epidemiology, Stanford University School of Medicine, Stanford, California, USA

    Ann Hsing

  21. James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institutions, Baltimore, Maryland, USA

    William Isaacs

  22. Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

    Rick A Kittles

  23. Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA

    Eric A Klein

  24. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA

    Leslie A Lange

  25. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA

    David Reich

  26. Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA

    Benjamin A Rybicki

  27. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Janet L Stanford & Charles Kooperberg

  28. Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA

    Victoria L Stevens

  29. Department of Epidemiology, Division of Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Sara S Strom

  30. Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.,

    John S Witte

  31. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

    Jianfeng Xu

  32. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA

    Christopher Haiman

  33. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA

    James G Wilson

  34. Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA

    Alex P Reiner

  35. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA

    Hua Tang

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  1. Noah Zaitlen
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Contributions

N.Z., B.P., S.S., G.B., A.G., B.J.V., C.H., J.G.W., C.K., D.S., A.P.R., H.T. and A.L.P. designed experiments. N.Z., J.Z., T.Y., A.T., S.P., H.T. and A.L.P. performed experiments. N.Z., S.S., C.H., J.G.W., C.K., D.S., A.P.R., H.T. and A.L.P. wrote the text. T.L.A., S.I.B., W.J.B., S.C., N.F., P.J.G., J.H., A.J.M.H., A.H., S.A.I., W.I., R.A.K., E.A.K., L.A.L., B.N., N.P., D.R., B.A.R., J.L.S., V.L.S., S.S.S., E.A.W., J.S.W. and J.X. provided data.

Corresponding authors

Correspondence to Noah Zaitlen, Hua Tang or Alkes L Price.

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The authors declare no competing financial interests.

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Zaitlen, N., Pasaniuc, B., Sankararaman, S. et al. Leveraging population admixture to characterize the heritability of complex traits. Nat Genet 46, 1356–1362 (2014). https://doi.org/10.1038/ng.3139

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