TY - JOUR
T1 - Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry
AU - Cornelis, Marilyn C.
AU - Qi, Lu
AU - Zhang, Cuilin
AU - Kraft, Peter
AU - Manson, Jo Ann
AU - Cai, Tianxi
AU - Hunter, David J.
AU - Hu, Frank B.
PY - 2009/4/21
Y1 - 2009/4/21
N2 - Background: Genome-wide association studies have identified novel type 2 diabetes loci, each of which has a modest impact on risk. Objective: To examine the joint effects of several type 2 diabetes risk variants and their combination with conventional risk factors on type 2 diabetes risk in 2 prospective cohorts. Design: Nested case-control study. Setting: United States. Participants: 2809 patients with type 2 diabetes and 3501 healthy control participants of European ancestry from the Health Professionals Follow-up Study and Nurses' Health Study. Measurements: A genetic risk score (GRS) was calculated on the basis of 10 polymorphisms in 9 loci. Results: After adjustment for age and body mass index (BMI), the odds ratio for type 2 diabetes with each point of GRS, corresponding to 1 risk allele, was 1.19 (95% Cl, 1.14 to 1.24) and 1.16 (Cl, 1.12 to 1.20) for men and women, respectively. Persons with a BMI of 30 kg/m2 or greater and a GRS in the highest quintile had an odds ratio of 14.06 (Cl, 8.90 to 22.18) compared with persons with a BMI less than 25 kg/m2 and a GRS in the lowest quintile after adjustment for age and sex. Persons with a positive family history of diabetes and a GRS in the highest quintile had an odds ratio of 9.20 (Cl, 5.50 to 15.40) compared with persons without a family history of diabetes and with a GRS in the lowest quintile. The addition of the GRS to a model of conventional risk factors improved discrimination by 1% (P < 0.001). Limitation: The study focused only on persons of European ancestry; whether GRS is associated with type 2 diabetes in other ethnic groups remains unknown. Conclusion: Although its discriminatory value is currently limited, a GRS that combines information from multiple genetic variants might be useful for identifying subgroups with a particularly high risk for type 2 diabetes. Primary Funding Source: National Institutes of Health.
AB - Background: Genome-wide association studies have identified novel type 2 diabetes loci, each of which has a modest impact on risk. Objective: To examine the joint effects of several type 2 diabetes risk variants and their combination with conventional risk factors on type 2 diabetes risk in 2 prospective cohorts. Design: Nested case-control study. Setting: United States. Participants: 2809 patients with type 2 diabetes and 3501 healthy control participants of European ancestry from the Health Professionals Follow-up Study and Nurses' Health Study. Measurements: A genetic risk score (GRS) was calculated on the basis of 10 polymorphisms in 9 loci. Results: After adjustment for age and body mass index (BMI), the odds ratio for type 2 diabetes with each point of GRS, corresponding to 1 risk allele, was 1.19 (95% Cl, 1.14 to 1.24) and 1.16 (Cl, 1.12 to 1.20) for men and women, respectively. Persons with a BMI of 30 kg/m2 or greater and a GRS in the highest quintile had an odds ratio of 14.06 (Cl, 8.90 to 22.18) compared with persons with a BMI less than 25 kg/m2 and a GRS in the lowest quintile after adjustment for age and sex. Persons with a positive family history of diabetes and a GRS in the highest quintile had an odds ratio of 9.20 (Cl, 5.50 to 15.40) compared with persons without a family history of diabetes and with a GRS in the lowest quintile. The addition of the GRS to a model of conventional risk factors improved discrimination by 1% (P < 0.001). Limitation: The study focused only on persons of European ancestry; whether GRS is associated with type 2 diabetes in other ethnic groups remains unknown. Conclusion: Although its discriminatory value is currently limited, a GRS that combines information from multiple genetic variants might be useful for identifying subgroups with a particularly high risk for type 2 diabetes. Primary Funding Source: National Institutes of Health.
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U2 - 10.7326/0003-4819-150-8-200904210-00008
DO - 10.7326/0003-4819-150-8-200904210-00008
M3 - Article
C2 - 19380854
AN - SCOPUS:65349192772
VL - 150
SP - 541
EP - 550
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 8
ER -
