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Ann Intern Med. 2009 Apr 21;150(8):541-50.

Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry.

Author information

  • 1Harvard School of Public Health, Channing Laboratory, Boston, MA 02115, USA.

Abstract

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% CI, 1.14 to 1.24) and 1.16 (CI, 1.12 to 1.20) for men and women, respectively. Persons with a BMI of 30 kg/m(2) or greater and a GRS in the highest quintile had an odds ratio of 14.06 (CI, 8.90 to 22.18) compared with persons with a BMI less than 25 kg/m(2) 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 (CI, 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.

Comment in

PMID:
19380854
[PubMed - indexed for MEDLINE]
PMCID:
PMC3825275
Free PMC Article

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