The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes.

We have developed a scale for AN that is easy to use, has high interobserver reliability in Mexican Americans, and correlates well with fasting insulin and BMI. This scale will permit longitudinal and cross-sectional evaluation of AN and will permit the evaluation of AN as a trait in genetic studies.

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Objective-To evaluate the impact of a school-based diabetes mellitus prevention program on lowincome fourth-grade Mexican American children.Design-A randomized controlled trial with 13 intervention and 14 control schools. Setting-Elementary schools in inner-city neighborhoods in San Antonio, Tex.Participants-Eighty percent of participants were Mexican American and 94% were from economically disadvantaged households. Baseline and follow-up measures were collected from 1419 (713 intervention and 706 control) and 1221 (619 intervention and 602 control) fourth-grade children, respectively. Intervention-The Bienestar Health Program consists of a health class and physical education curriculum, a family program, a school cafeteria program, and an after-school health club. The objectives are to decrease dietary saturated fat intake, increase dietary fiber intake, and increase physical activity.Main Outcome Measures-The primary end point was fasting capillary glucose level, and the secondary end points were percentage of body fat, physical fitness level, dietary fiber intake, and dietary saturated fat intake. Fasting capillary glucose level, bioelectric impedance, modified Harvard step test, three 24-hour dietary recalls, weight, and height were collected at baseline and 8 months later.Results-Children in the intervention arm attended an average of 32 Bienestar sessions. Mean fasting capillary glucose levels decreased in intervention schools and increased in control schools after adjusting for covariates (−2.24 mg/dL [0.12 mmol/L]; 95% confidence interval, −6.53 to 2.05 [−0.36 to 0.11 mmol/L]; P = .03). Fitness scores (P = .04) and dietary fiber intake (P = .009) significantly increased in intervention children and decreased in control children. Percentage of body fat (P = .56) and dietary saturated fat intake (P = .52) did not differ significantly between intervention and control children.

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