Joan E. Hilner

Cardiovascular risk factors in young adults: The CARDIA baseline monograph

Gary R. Cutter, PhD*(1), Gregory L. Burke, MD (2), Alan R. Dyer, PhD (3), Gary D. Friedman, MD (4), Joan E. Hilner, MPH, MA, RD (5), Glenn H. Hughes, PhD (6), Stephen B. Hulley, MD (7), David R. Jacobs Jr., PhD (2), Kiang Liu, PhD (3), Teri A. Manolio, MD, MHS (8), Albert Oberman, MD (9), Laura L. Perkins, PhD (5), Peter J. Savage, MD (8), Joyce R. Serwitz, MEd (5), Stephen Sidney, MD (4), Lynne E. Wagenknecht, Dr PH (5)

Body image among men and women in a biracial cohort : The CARDIA study

OBJECTIVE To examine body image in a population-based, biracial cohort. METHOD Body image measures were obtained on 1,837 men (45% Black) and 1,895 women (51% Black) in the CARDIA study. Subscales of the Multidimensional Body Self-Relations Questionnaire (Appearance Evaluation and Appearance Orientation) and a measure of body size dissatisfaction were obtained. RESULTS Blacks were more invested in appearance than Whites and women were more invested than men. Women were more dissatisfied with size and overall appearance than men, and White men were more dissatisfied with appearance than Black men. Black and White women were similarly dissatisfied with size and appearance. However, after adjustment for age, body mass index, and education, Black women were more satisfied with both dimensions than White women. Obesity was strongly associated with body dissatisfaction across all gender-ethnicity groups. DISCUSSION Significant differences in body image were apparent by gender and ethnicity, and different patterns were evident depending on the dimension considered.

Differences in weight gain in relation to race, gender, age and education in young adults: The CARDIA study

OBJECTIVE To assess ethnic differences in weight gain in young adults. DESIGN Five-year weight change was assessed in 4207 young adults initially aged 18-30 years at the CARDIA Study baseline examination (1985-1986). RESULTS Weight gain was significantly (p < 0.0001) greater in black versus white men (13.2 versus 9.1 lb) and in black versus white women (13.2 versus 7.4 lb). Baseline weight and year-five weight in all race and gender groups were strongly associated, suggesting a high degree of tracking of adiposity during young adulthood. Greater weight gain was noted in participants reporting baseline education of high school or less versus college graduates in black women (14.4 versus 10.0 lb, p < 0.05), white women (10.2 versus 5.2 lb, p < 0.0001) and white men (10.2 versus 7.8 lb, p < 0.001). Significantly greater weight gain was observed in younger (18-24 years) versus older (25-30 years) men, but no age-related difference was seen in women. The racial differences in weight gain remained after adjustment for age and level of education. The above trends were confirmed for other measures of body size, i.e. body mass index and skinfold thickness. CONCLUSION These data indicate that young adults are at high risk of weight gain, and that weight gain was greatest among African Americans and among less educated participants. These high-risk groups can be identified and targeted for primary prevention of adult obesity in addition to population wide efforts that will be required to counteract the secular trend of increased obesity observed in US adults.

A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3.

OBJECTIVE— The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled and genotyped a large collection of multiplex families for the purpose of mapping genomic regions linked to type 1 diabetes. In the current study, we tested for evidence of loci associated with type 1 diabetes utilizing genome-wide linkage scan data and family-based association methods. RESEARCH DESIGN AND METHODS— A total of 2,496 multiplex families with type 1 diabetes were genotyped with a panel of 6,090 single nucleotide polymorphisms (SNPs). Evidence of association to disease was evaluated by the pedigree disequilibrium test. Significant results were followed up by genotyping and analyses in two independent sets of samples: 2,214 parent-affected child trio families and a panel of 7,721 case and 9,679 control subjects. RESULTS— Three of the SNPs most strongly associated with type 1 diabetes localized to previously identified type 1 diabetes risk loci: INS, IFIH1, and KIAA0350. A fourth strongly associated SNP, rs876498 (P = 1.0 × 10−4), occurred in the sixth intron of the UBASH3A locus at chromosome 21q22.3. Support for this disease association was obtained in two additional independent sample sets: families with type 1 diabetes (odds ratio [OR] 1.06 [95% CI 1.00–1.11]; P = 0.023) and case and control subjects (1.14 [1.09–1.19]; P = 7.5 × 10−8). CONCLUSIONS— The T1DGC 6K SNP scan and follow-up studies reported here confirm previously reported type 1 diabetes associations at INS, IFIH1, and KIAA0350 and identify an additional disease association on chromosome 21q22.3 in the UBASH3A locus (OR 1.10 [95% CI 1.07–1.13]; P = 4.4 × 10−12). This gene and its flanking regions are now validated targets for further resequencing, genotyping, and functional studies in type 1 diabetes.

Genome-wide scan for linkage to type 1 diabetes in 2,496 multiplex families from the Type 1 Diabetes Genetics Consortium.

OBJECTIVE Type 1 diabetes arises from the actions of multiple genetic and environmental risk factors. Considerable success at identifying common genetic variants that contribute to type 1 diabetes risk has come from genetic association (primarily case-control) studies. However, such studies have limited power to detect genes containing multiple rare variants that contribute significantly to disease risk. RESEARCH DESIGN AND METHODS The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled a collection of 2,496 multiplex type 1 diabetic families from nine geographical regions containing 2,658 affected sib-pairs (ASPs). We describe the results of a genome-wide scan for linkage to type 1 diabetes in the T1DGC family collection. RESULTS Significant evidence of linkage to type 1 diabetes was confirmed at the HLA region on chromosome 6p21.3 (logarithm of odds [LOD] = 213.2). There was further evidence of linkage to type 1 diabetes on 6q that could not be accounted for by the major linkage signal at the HLA class II loci on chromosome 6p21. Suggestive evidence of linkage (LOD ≥2.2) was observed near CTLA4 on chromosome 2q32.3 (LOD = 3.28) and near INS (LOD = 3.16) on chromosome 11p15.5. Some evidence for linkage was also detected at two regions on chromosome 19 (LOD = 2.84 and 2.54). CONCLUSIONS Five non–HLA chromosome regions showed some evidence of linkage to type 1 diabetes. A number of previously proposed type 1 diabetes susceptibility loci, based on smaller ASP numbers, showed limited or no evidence of linkage to disease. Low-frequency susceptibility variants or clusters of loci with common alleles could contribute to the linkage signals observed.

Correlates of fasting insulin levels in young adults: The cardia study

Elevated fasting insulin is an independent risk factor for hyperlipidemia, hypertension, and cardiovascular disease, but determinants of insulin other than age and body mass remain poorly described. Potentially modifiable factors associated with insulin were identified by correlating anthropometric, dietary and physical activity data in the CARDIA cohort of 2643 black and 2472 white men and women aged 18-30 years. Insulin was positively correlated with serum glucose, body mass index (BMI), skinfold thickness, waist/hip ratio and sucrose intake, and negatively correlated with heavy physical activity score, treadmill exercise duration, and magnesium intake (each p less than 0.01). After adjustment for other covariates, the positive association of insulin with waist/hip ratio, skinfold thickness, and sucrose intake remained in the group as a whole, as did the negative associations with magnesium and treadmill duration. These relationships provide insight into potentially modifiable factors affecting insulin levels, and should be considered in interpreting associations between insulin levels and cardiovascular disease.

Seven-year trends in pasma low-density-lipoprotein-cholesterol in young Adults: the CARDIA Study

To identify determinants of recent secular trends in lipids and characterize their influence on age-related increases in LDL-cholesterol, we examined a cohort of black and white men and women aged 18-30 in 1985-1986. Secular trends were determined by comparing participants aged 25-30 at baseline with those aged 25-30 at year 7 (2788 and 1395 participants, respectively). LDL-cholesterol was lower among those 25-30 at year 7 (5.9 to 10.2 mg/dL, depending on race-sex group; P < 0.001); weight was higher (8.3 to 12.5 lb; P < 0.001); Keys score was lower (-4.2 to -7.3 units; P < 0.001); and use of oral contraceptives was greater (white women only, P < 0.01). Among 4086 participants followed for 7 years, LDL-cholesterol changed little or decreased, despite substantial weight increases in all groups (11.6 to 19.0 lb; P < 0.001). Keys scores decreased by 6.1 to 8.0 units, and use of oral contraceptives decreased (P < 0.001). Declining secular trends in LDL-cholesterol occurred despite upward trends in weight; the decline was associated with lower dietary fat and cholesterol and offset expected age-related increases in LDL-cholesterol.

Regional Disparities in the Incidence of Elevated Blood Pressure Among Young Adults The CARDIA Study

BACKGROUND Within the United States, little is known about regional disparities in blood pressure (BP), their changes over time, or explanations for their existence. METHODS AND RESULTS A population-based cohort of 5115 black and white men and women, 18 to 30 years old in 1985-1986 (balanced on age, race, sex, and education), was followed up for 7 years in four centers: Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif. Differences in elevated BP (EBP) prevalence among centers at years 0, 2, 5, and 7 and in 7-year incidence of EBP were assessed. Sociodemographic and dietary variables, physical activity, weight, smoking, and alcohol were considered. At year 0, no regional differences were seen. Seven years later, there was marked variability in prevalence of EBP overall and for both black and white men, from a low in Chicago (9% for black men and 5% for white men) to a high in Birmingham (25% for black men and 14% for white men). Birmingham also had the highest 7-year incidence (11%) and overall prevalence at year 7 (14%). The adjusted odds ratios, with Birmingham as referent (95% CIs), for 7-year incidence of EBP overall were 0.38 (0.24, 0.60) for Chicago, 0.37 (0.24, 0.57) for Minneapolis, and 0.74 (0.52, 1.07) for Oakland. CONCLUSIONS Regional disparities are absent at baseline but become apparent as the cohort ages. These differences are not fully explained by the available behavioral and sociodemographic characteristics.

HLA genotyping in the international Type 1 Diabetes Genetics Consortium

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75—S87. http:// ctj.sagepub.com

Overview of the Type I Diabetes Genetics Consortium

The Type I Diabetes Genetics Consortium (T1DGC) is an international, multicenter research program with two primary goals. The first goal is to identify genomic regions and candidate genes whose variants modify an individuals risk of type I diabetes (T1D) and help explain the clustering of the disease in families. The second goal is to make research data available to the research community and to establish resources that can be used by, and that are fully accessible to, the research community. To facilitate the access to these resources, the T1DGC has developed a Consortium Agreement (http://www.t1dgc.org) that specifies the rights and responsibilities of investigators who participate in Consortium activities. The T1DGC has assembled a resource of affected sib-pair families, parent–child trios, and case–control collections with banks of DNA, serum, plasma, and EBV-transformed cell lines. In addition, both candidate gene and genome-wide (linkage and association) studies have been performed and displayed in T1DBase (http://www.t1dbase.org) for all researchers to use in their own investigations. In this supplement, a subset of the T1DGC collection has been used to investigate earlier published candidate genes for T1D, to confirm the results from a genome-wide association scan for T1D, and to determine associations with candidate genes for other autoimmune diseases or with type II diabetes that may be involved with β-cell function.