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Genetic and environmental components of family history in type 2 diabetes

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Abstract

Family history of diabetes is a major risk factor for type 2 diabetes (T2D), but whether this association derives from shared genetic or environmental factors is unclear. To address this question, we developed a statistical framework that models four components of variance, including known and unknown genetic and environmental factors, using a liability threshold model. Focusing on parental history, we simulated case–control studies with two first-degree relatives for each individual, assuming 50 % genetic similarity and a range of values of environmental similarity. By comparing the association of parental history with T2D in our simulations to case–control studies of T2D nested in the Nurses’ Health Study and Health Professionals Follow-up Study, we estimate that first-degree relatives have a correlation of 23 % (95 % CI 15–27 %) in their environmental contribution to T2D liability and that this shared environment is responsible for 32 % (95 % CI 24–36 %) of the association between parental history and T2D, with the remainder due to shared genetics. Estimates are robust to varying model parameter values and our framework can be extended to different definitions of family history. In conclusion, we find that the association between parental history and T2D derives from predominately genetic but also environmental effects.

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Acknowledgments

This work was supported by the National Institute of Environmental Health (R21ES020754-01). The Nurses’ Health Study/Health Professionals Follow-up Study Type 2 Diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS funded as part of the Gene-Environment Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment, and Health Initiative. Additional funding was provided by the National Cancer Institute (P01CA087969, P01CA055075) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845).

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Authors and Affiliations

  1. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore, Suite 1400, Chicago, IL, 60611, USA

    Marilyn C. Cornelis

  2. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    Marilyn C. Cornelis & Frank B. Hu

  3. Department of Medicine, Lung Biology Center, University of California San Francisco, San Francisco, CA, USA

    Noah Zaitlen

  4. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Frank B. Hu, Peter Kraft & Alkes L. Price

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

    Peter Kraft & Alkes L. Price

  6. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Alkes L. Price

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  1. Marilyn C. Cornelis
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  2. Noah Zaitlen
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  3. Frank B. Hu
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Correspondence to Marilyn C. Cornelis.

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Cornelis, M.C., Zaitlen, N., Hu, F.B. et al. Genetic and environmental components of family history in type 2 diabetes. Hum Genet 134, 259–267 (2015). https://doi.org/10.1007/s00439-014-1519-0

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