Dataset Information

How Can Genetic Studies Help Us to Understand Links Between Birth Weight and Type 2 Diabetes?

ABSTRACT: In observational epidemiology, both low and high birth weights are associated with later type 2 diabetes. The mechanisms underlying the associations are poorly understood. We review evidence for the roles of genetic and non-genetic factors linking both sides of the birth weight distribution to risk of type 2 diabetes, focusing on contributions made by the most recent genome-wide association studies (GWAS) of birth weight.There are now nine genetic loci robustly implicated in both fetal growth and type 2 diabetes. At many of these, the same alleles are associated both with a higher risk of type 2 diabetes and a lower birth weight. This supports the Fetal Insulin Hypothesis and reflects a general pattern for type 2 diabetes susceptibility alleles: genome-wide, there is an inverse genetic correlation with birth weight, and initial estimates suggest genetic factors explain a large part of the covariance between the two traits. However, the associations at individual loci show heterogeneity; some fetal risk alleles are associated with higher birth weight. For most of these, the association reflects their correlation with the maternal risk allele which raises maternal glucose, thus increasing fetal insulin-mediated growth. GWAS have improved our understanding of the mechanisms underlying associations between type 2 diabetes and birth weight but questions remain about the relative importance of genetic versus non-genetic factors and of maternal versus fetal genotypes. To answer these questions, future work will require well-powered analyses of parents and offspring.

SUBMITTER: Beaumont RN

PROVIDER: S-EPMC5350261 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

How Can Genetic Studies Help Us to Understand Links Between Birth Weight and Type 2 Diabetes?

Beaumont Robin N RN Horikoshi Momoko M McCarthy Mark I MI Freathy Rachel M RM

Current diabetes reports 20170401 4

<h4>Purpose of review</h4>In observational epidemiology, both low and high birth weights are associated with later type 2 diabetes. The mechanisms underlying the associations are poorly understood. We review evidence for the roles of genetic and non-genetic factors linking both sides of the birth weight distribution to risk of type 2 diabetes, focusing on contributions made by the most recent genome-wide association studies (GWAS) of birth weight.<h4>Recent findings</h4>There are now nine geneti ...[more]

PMID: 28293907

Similar Datasets

Project description:Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

Dataset Information

How Can Genetic Studies Help Us to Understand Links Between Birth Weight and Type 2 Diabetes?

Publications

How Can Genetic Studies Help Us to Understand Links Between Birth Weight and Type 2 Diabetes?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure