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Little is known about the genetic influence on BMI trajectory throughout adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI-associated variants among 9,971 women and 6,405 men of European ancestry. Serial measures of BMI were assessed from 18 (women) or 21 (men) years to 85 years of age. We also examined BMI change in early (from 18 or 21 to 45 years of age), middle (from 45 to 65 years of age), and late adulthood (from 65 to 80 years of age). GRS was positively associated with BMI across all ages, with stronger associations in women than in men. The associations increased from early to middle adulthood, peaked at 45 years of age in men and at 60 years of age in women (0.91 and 1.35 kg/m2 per 10-allele increment, respectively) and subsequently declined in late adulthood. For women, each 10-allele increment in the GRS was associated with an average BMI gain of 0.54 kg/m2 in early adulthood, whereas no statistically significant association was found for BMI change in middle or late adulthood or for BMI change in any life period in men. Our findings indicate that genetic predisposition exerts a persistent effect on adiposity throughout adult life and increases early adulthood weight gain in women. [ABSTRACT FROM AUTHOR]

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/m2 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/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 (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. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the associations between common variations in the IL6R gene and circulating interleukin (IL)-6 levels and diabetes risk. RESEARCH DESIGN AND METHODS--We determined 10 linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) (SNP1 to SNP10) for the IL6R gene in a nested case-control study of 672 diabetic and 1,058 healthy European Caucasian women (IL-6 levels were measured in a subgroup of 1,348 women). RESULTS--In both control and diabetic patients, polymorphisms within an LD block spanning ∼42 kb were significantly associated with plasma IL-6 levels. A missense variant SNP7 in exon 9 (rs8192284, Asp358Ala) showed the strongest association (P = 0.0005 in control and P = 0.004 in case subjects). The corresponding false-discovery rates, which accounts for multiple testing, were 0.008 and 0.02, respectively. We inferred five common haplotypes to capture 94% allele variance of the LD block using SNP5, -7, -8, -9, and -10. Compared with the most common haplotype 12111 (one codes the common and two codes the minor alleles), haplotypes 11211 [difference in log(IL-6) = -0.11 (95% CI -0.23 to -0.01); P = 0.01] and 21122 (-0.15 [-0.27 to -0.03]; P = 0.01) were associated with significantly lower IL-6 levels (global test, P = 0.01). However, IL6R genotypes were not significantly associated with the risk of type 2 diabetes. CONCLUSIONS--IL6R genetic variations, especially SNP7 (rs8192284, Asp358Ala), were significantly associated with plasma IL-6 levels but not with diabetes risk in women. The strong associations between IL6R genetic variability and IL-6 concentrations deserve further investigation. Diabetes 56: 3075-3081, 2007 [ABSTRACT FROM AUTHOR]