Genetic and environmental components of family history in type 2 diabetes

Marilyn C. Cornelis*, Noah Zaitlen, Frank B. Hu, Peter Kraft, Alkes L. Price

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)259-267
Number of pages9
JournalHuman Genetics
Volume134
Issue number2
DOIs
StatePublished - Jan 13 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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