Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges
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Causal factors underlying diabetes risk informed by Mendelian randomisation analysis : evidence, opportunities and challenges. / Yuan, Shuai; Merino, Jordi; Larsson, Susanna C.
In: Diabetologia, Vol. 66, 2023, p. 800-812.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Causal factors underlying diabetes risk informed by Mendelian randomisation analysis
T2 - evidence, opportunities and challenges
AU - Yuan, Shuai
AU - Merino, Jordi
AU - Larsson, Susanna C.
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development. Graphical abstract: [Figure not available: see fulltext.].
AB - Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development. Graphical abstract: [Figure not available: see fulltext.].
KW - Causality
KW - Diabetes
KW - Mendelian randomisation
KW - Review
KW - Risk factor
U2 - 10.1007/s00125-023-05879-7
DO - 10.1007/s00125-023-05879-7
M3 - Review
C2 - 36786839
AN - SCOPUS:85147983191
VL - 66
SP - 800
EP - 812
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
ER -
ID: 337597782