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IGF-1 and cardiometabolic diseases: a Mendelian randomisation study

Diabetologia, 2020-09, Vol.63 (9), p.1775-1782 [Peer Reviewed Journal]

The Author(s) 2020 ;The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;ISSN: 0012-186X ;ISSN: 1432-0428 ;EISSN: 1432-0428 ;DOI: 10.1007/s00125-020-05190-9 ;PMID: 32548700

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Title:
IGF-1 and cardiometabolic diseases: a Mendelian randomisation study
Author: Larsson, Susanna C. ; Michaëlsson, Karl ; Burgess, Stephen
Subjects: Adult ; Aged ; Body Height - genetics ; Cardiac arrhythmia ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Causality ; Congestive heart failure ; Coronary artery ; Coronary vessels ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - genetics ; Female ; Fibrillation ; Heart failure ; Human Physiology ; Humans ; IGF-1 ; Insulin-like growth factor ; Insulin-like growth factor I ; Insulin-Like Growth Factor I - genetics ; Insulin-Like Growth Factor I - metabolism ; Insulin-like growth factors ; Internal Medicine ; Male ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Mendelian randomisation ; Mendelian Randomization Analysis ; Metabolic Diseases ; Metabolic Syndrome - epidemiology ; Metabolic Syndrome - genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Single-nucleotide polymorphism ; Type 2 diabetes
Is Part Of: Diabetologia, 2020-09, Vol.63 (9), p.1775-1782
Description: Aims/hypothesis Abnormal serum IGF-1 levels are associated with an increased risk of type 2 diabetes and cardiovascular disease. However, the causal role of IGF-1 levels within the normal range in cardiometabolic disease remains unclear. We employed Mendelian randomisation to explore the associations between genetically predicted serum IGF-1 levels and cardiometabolic diseases. Methods Serum IGF-1 levels were predicted using 416 SNPs associated with IGF-1 levels among 358,072 individuals in UK Biobank. Genetic association estimates for the outcomes were obtained from consortia of type 2 diabetes (74,124 cases, 824,006 controls), coronary artery disease (60,801 cases, 123,504 controls), heart failure (47,309 cases, 930,014 controls), atrial fibrillation (65,446 cases, 522,744 controls), and ischaemic stroke (60,341 cases, 454,450 controls). Results Genetic predisposition to elevated serum IGF-1 levels was associated with higher risk of type 2 diabetes and coronary artery disease. The OR (95% CI) per SD increment in IGF-1 level was 1.14 (1.05, 1.24) for type 2 diabetes and 1.09 (1.02, 1.16) for coronary artery disease. The association between IGF-1 and coronary artery disease was attenuated after adjustment for type 2 diabetes (OR 1.06 [95% CI 1.00, 1.13]), suggesting that the association may be partly mediated via type 2 diabetes. There was limited evidence of associations between IGF-1 levels and heart failure, atrial fibrillation and ischaemic stroke. Conclusions/interpretation This study found evidence that increased IGF-1 levels may be causally associated with higher risk of type 2 diabetes. Graphical abstract
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0012-186X
ISSN: 1432-0428
EISSN: 1432-0428
DOI: 10.1007/s00125-020-05190-9
PMID: 32548700
Source: MEDLINE
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IGF-1 and cardiometabolic diseases: a Mendelian randomisation study

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