Cornelis, M. C. et al. Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry. Ann. Intern. Med. 150, 541–550 (2009).

New research has examined the discriminatory value of a genetic risk score, which includes several alleles linked to type 2 diabetes mellitus. “When combining variants into a single genetic score we observed that each additional risk variant was associated with an approximately 16% to 19% increased risk of type 2 diabetes,” describes Marilyn Cornelis from the Harvard School of Public Health. Furthermore, combining this score with conventional risk factors can identify people with a particularly high risk for type 2 diabetes mellitus.

The highest scores combined with a BMI ≥30 kg/m2 conferred a considerably increased risk of type 2 diabetes...

Genome-wide association studies have found genetic factors linked to a person's risk for type 2 diabetes mellitus. “The risk attributable to any one of these loci, however, is very modest and unlikely to have important clinical utility,” Cornelis comments. Consequently, Cornelis' team investigated the effect of combining both genetic and conventional risk factors for type 2 diabetes mellitus.

The US study included 2,809 patients with type 2 diabetes mellitus (1,297 men from the Health Professionals Follow-up Study and 1,612 women from the Nurses' Health study) and 3,501 healthy age-matched controls, all of European ancestry. Information on conventional risk factors (age, BMI, family history of type 2 diabetes mellitus) was collected and blood samples were taken for genotyping. “We devised a simple genetic risk score by adding up the number of risk variants at each loci, and examined the risk of type 2 diabetes associated with this score,” Cornelis explains.

The genetic risk score was associated with type 2 diabetes mellitus even after accounting for the effects of conventional risk factors; higher scores indicated a greater risk of developing the disease. The highest scores combined with a BMI ≥30 kg/m2 conferred a considerably increased risk of type 2 diabetes mellitus compared with the lowest scores and a BMI <25 kg/m2. A similar pattern was observed in relation to family history of diabetes mellitus. However, Cornelis notes that “the discriminatory value of the genetic risk score above and beyond conventional risk factors is limited”.