Genetic and environmental components of family history in type 2 diabetes

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.

Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies

“…Despite increasing evidence suggesting that T2D is associated with increased risk of colorectal cancer (2)(3)(4)(5), no previous study has investigated whether family history of diabetes, a strong risk factor for T2D, might be related to colorectal cancer. An estimation by a statistical liability threshold model suggests that shared genetics is responsible for 68% of the association between parental history and T2D, with the remainder due to shared environmental factors (6), which is consistent with reports from empirical epidemiologic studies (28,29). However, in the EPIC-InterAct study, adiposity, lifestyle, and a genetic risk score comprising 35 single-nucleotide polymorphisms associated with T2D only accounted for a small proportion of the risk increase related to family history of diabetes, leaving the majority of the risk unexplained, and the genetic risk score alone explained only 2% of the family history-associated T2D risk (9).…”

“…A family history of diabetes reflects both genetic background and shared environmental risk factors (6) and is a risk factor for a range of metabolic abnormalities (7) and development of T2D (8,9). Interestingly, an analysis in the EPIC-InterAct study showed that established lifestyle and genetic risk factors only explained a marginal proportion of the excess T2D risk associated with family history, highlighting the potential independence of family history as a risk factor (9).…”

Family history of diabetes in both parents is strongly associated with impaired residual β‐cell function in Japanese type 2 diabetes patients

“…Family history of diabetes is a reflection of both genetic components and environmental components, such as behavior and lifestyle (e.g., diet and exercise), that are shared, to some extent, by a family. Regarding genetic factors, recent advances in genetic technologies have revealed a growing number of genes that are related to type 2 diabetes; to date, >120 distinct genetic loci, with >150 variants, with potential involvement in the pathogenesis of type 2 diabetes have been identified.…”

Association between Dichlorodiphenyldichloroethylene in the Serum and Adipose Tissue with Type 2 Diabetes: A Systematic Review and Meta-Analysis

“…Also, the International Diabetes Federation (IDF) has reported that in 2013, 382 million human (8.3%) of the world's population suffered from diabetes that 175 million of them have not been diagnosed and has predicted that almost 592 million human (10.1%) will be affected to this disease by the year 2035 (IDF, 2011). This increasing process is assigned to the environmental and genetic factors (Das, 2010;Cornelis, Zaitlen, Hu, Kraft, & Price, 2015). Diabetes risk factors include low motility, obesity, genetics, race, age, hypertension, high triglycerides and low high density lipoproteins (HDL) (Katzmarzyk, 2008;Group, 2013).…”