Human Genetics

, Volume 134, Issue 2, pp 259–267 | Cite as

Genetic and environmental components of family history in type 2 diabetes

  • Marilyn C. Cornelis
  • Noah Zaitlen
  • Frank B. Hu
  • Peter Kraft
  • Alkes L. Price
Original Investigation

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.

Supplementary material

439_2014_1519_MOESM1_ESM.doc (238 kb)
Supplementary material 1 (DOC 238 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Marilyn C. Cornelis
    • 1
    • 2
  • Noah Zaitlen
    • 3
  • Frank B. Hu
    • 2
    • 4
  • Peter Kraft
    • 4
    • 5
  • Alkes L. Price
    • 4
    • 5
    • 6
  1. 1.Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of NutritionHarvard School of Public HealthBostonUSA
  3. 3.Department of Medicine, Lung Biology CenterUniversity of California San FranciscoSan FranciscoUSA
  4. 4.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  5. 5.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  6. 6.Broad Institute of MIT and HarvardCambridgeUSA

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