Dataset Information

Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research.

ABSTRACT: Epidemiologists have for many decades reported on the patterns and distributions of diabetes within and between populations and have helped to elucidate the aetiology of the disease. This has helped raise awareness of the tremendous burden the disease places on individuals and societies; it has also identified key risk factors that have become the focus of diabetes prevention trials and helped shape public health recommendations. Recent developments in affordable high-throughput genetic and molecular phenotyping technologies have driven the emergence of a new type of epidemiology with a more mechanistic focus than ever before. Studies employing these technologies have identified gene variants or causal loci, and linked these to other omics data that help define the molecular processes mediating the effects of genetic variation in the expression of clinical phenotypes. The scale of these epidemiological studies is rapidly growing; a trend that is set to continue as the public and private sectors invest heavily in omics data generation. Many are banking on this massive volume of diverse molecular data for breakthroughs in drug discovery and predicting sensitivity to risk factors, response to therapies and susceptibility to diabetes complications, as well as the development of disease-monitoring tools and surrogate outcomes. To realise these possibilities, it is essential that omics technologies are applied to well-designed epidemiological studies and that the emerging data are carefully analysed and interpreted. One might view this as next-generation epidemiology, where complex high-dimensionality data analysis approaches will need to be blended with many of the core principles of epidemiological research. In this article, we review the literature on omics in diabetes epidemiology and discuss how this field is evolving. Graphical abstract.

SUBMITTER: Franks PW

PROVIDER: S-EPMC7641957 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research.

Franks Paul W PW Pomares-Millan Hugo H

Diabetologia 20200825 12

Epidemiologists have for many decades reported on the patterns and distributions of diabetes within and between populations and have helped to elucidate the aetiology of the disease. This has helped raise awareness of the tremendous burden the disease places on individuals and societies; it has also identified key risk factors that have become the focus of diabetes prevention trials and helped shape public health recommendations. Recent developments in affordable high-throughput genetic and mole ...[more]

PMID: 32840675

Similar Datasets

Project description:The incidence of narcolepsy type 1 (NT1) increased in Sweden following the 2009-2010 mass-vaccination with the influenza Pandemrix-vaccine. NT1 has been associated with Human leukocyte antigen (HLA) DQB1*06:02 but full high-resolution HLA-typing of all loci in vaccine-induced NT1 remains to be done. Therefore, here we performed HLA typing by sequencing HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1 and DPB1 in 31 vaccine-associated NT1 patients and 66 of their first-degree relatives (FDR), and compared these data to 636 Swedish general population controls (GP). Previously reported disease-related alleles in the HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 extended haplotype were increased in NT1 patients (34/62 haplotypes, 54.8%) compared to GP (194/1272 haplotypes, 15.3%, p = 6.17E-16). Indeed, this extended haplotype was found in 30/31 patients (96.8%) and 178/636 GP (28.0%). In total, 15 alleles, four extended haplotypes, and six genotypes were found to be increased or decreased in frequency among NT1 patients compared to GP. Among subjects with the HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02-DQB1*06:02 haplotype, a second DRB4*01:03:01-DRB1*04:01:01-DQA1*03:02//*03:03:01-DQB1*03:01:01 haplotype (p = 2.02E-2), but not homozygosity for DRB1*15:01:01-DQB1*06:02:01 (p = 7.49E-1) conferred association to NT1. Alleles with increased frequency in DQA1*01:02:01 (p = 1.07E-2) and DQA1*03:02//*03:03:01 (p = 3.26E-2), as well as with decreased frequency in DRB3*01:01:02 (p = 8.09E-3), DRB1*03:01:01 (p = 1.40E-2), and DQB1*02:01:01 (p = 1.40E-2) were found among patients compared to their FDR. High-resolution HLA sequencing in Pandemrix-associated NT1 confirmed the strong association with the DQB1*06:02:01-containing haplotype but also revealed an increased association to the not previously reported extended HLA-DRB4*01:03:01-DRB1*04:01:01-DQA1*03:02//*03:03:01-DQB1*03:01:01 haplotype. High-resolution HLA typing should prove useful in dissecting the immunological mechanisms of vaccination-associated NT1.

Dataset Information

Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research.

Publications

Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets