Publications by authors named "Joan Hilner"
The Type 1 Diabetes Genetics Consortium (T1DGC) comprised groups of investigators from many countries throughout the world, with a common goal of identifying genes predisposing to type 1 diabetes. The T1DGC ascertained and collected samples from families with two or more affected siblings with type 1 diabetes and generated a broad array of clinical, genetic, and immunologic data. The T1DGC Autoantibody Workshop was designed to distribute data for analyses to discover genes associated with autoantibodies in those with type 1 diabetes.
View Article and Find Full Text PDFObjective: Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions.
View Article and Find Full Text PDFBackground: and
Purpose: Three network laboratories measured antibodies to islet autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were measured by similar, but not identical, methods in samples from participants in the Type 1 Diabetes Genetics Consortium (T1DGC).
Methods: All laboratories used radiobinding assays to detect antibodies to in vitro transcribed and translated antigen, but with different local standards, calibrated against the World Health Organization (WHO) reference reagent.
Background: and
Purpose: This article describes several ethical, legal, and social issues typical of international genetics biobanking, as encountered in the Type 1 Diabetes Genetics Consortium (T1DGC).
Methods: By studying the examples set and lessons learned from other international biobanking studies and by devoting considerable time and resources to identifying, addressing, and continually monitoring ethical and regulatory concerns, T1DGC was able to minimize the problems reported by some earlier studies.
Conclusions: Several important conclusions can be drawn based on the experience in this study: (1) Basic international standards for research ethics review and informed consent are broadly consistent across developed countries.
Background: When collecting phenotypic data in clinics across the globe, the Type 1 Diabetes Genetics Consortium (T1DGC) used several techniques that ensured consistency, completeness, and accuracy of the data.
Purpose: The aim of this article is to describe the procedures used for collection, entry, processing, and management of the phenotypic data in this international study.
Methods: The T1DGC ensured the collection of high quality data using the following procedures throughout the entire study period.
Background And Purpose: The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide.
Methods: T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center.
Background: and
Purpose: To yield large amounts of DNA for many genotype analyses and to provide a renewable source of DNA, the Type 1 Diabetes Genetics Consortium (T1DGC) harvested DNA and peripheral blood mononuclear cells (PBMCs) from individuals with type 1 diabetes and their family members in several regions of the world.
Methods: DNA repositories were established in Asia-Pacific, Europe, North America, and the United Kingdom. To address region-specific needs, different methods and sample processing techniques were used among the laboratories to extract and to quantify DNA and to establish Epstein-Barr virus transformed cell lines.
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.
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.
View Article and Find Full Text PDFObjective: 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).
Purpose: To study adiponectin, a circulating adipocytokine secreted by adipocytes inversely associated with diabetes and insulin resistance, and factors affecting its levels in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Methods: Adiponectin in serum was measured by radioimmunoassay in 3355 participants (ages: 23-45 years) categorized by fasting glucose levels as normal, impaired fasting glucose, or diabetes mellitus.
Results: Levels of adiponectin were higher in women, in white participants, and with age.
Background: Whole grain consumption may influence insulin through beneficial effects on satiety and body weight, intestinal absorption, or the action of specific nutrients or constituents.
Design And Methods: We examined the associations of whole grain intake, assessed by a diet history interview at baseline (year 0) and year 7, with body mass index (BMI), waist-hip ratio (WHR), and fasting insulin in 3,627 Black and White adults in the Coronary Artery Risk Development in Young Adults Study (CARDIA). We estimated year 0 and year 7 cross-sectional associations accounting for correlation between years using repeated measures regression.