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Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes : Mendelian randomization study

Larsson, Susanna C.; Scott, Robert A.; Traylor, Matthew; Langenberg, Claudia; Hindy, George LU ; Melander, Olle LU ; Orho-Melander, Marju LU ; Seshadri, Sudha; Wareham, Nicholas J and Markus, Hugh S. (2017) In Neurology 89(5). p.454-460
Abstract

Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes. Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNPstroke associations were derived from... (More)

Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes. Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNPstroke associations were derived from METASTROKE and the Stroke Genetics Network (n 5 18,476 ischemic stroke cases and 37,296 controls). Results: Conventional MR analysis showed associations between genetically predicted T2D and large artery stroke (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.16-1.40, p 5 3.3 3 1027) and small vessel stroke (OR 1.21, 95% CI 1.10-1.33, p 5 8.9 3 1025) but not cardioembolic stroke (OR 1.06, 95% CI 0.97-1.15, p 5 0.17). The association of T2D with large artery stroke but not small vessel stroke was consistent in a sensitivity analysis using the weighted median method, and there was no evidence of pleiotropy. Genetically predicted fasting glucose and fasting insulin levels and BMI were not statistically significantly associated with any ischemic stroke subtype.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
89
issue
5
pages
7 pages
publisher
American Academy of Neurology
external identifiers
  • scopus:85026552471
  • wos:000406599900013
ISSN
0028-3878
DOI
10.1212/WNL.0000000000004173
language
English
LU publication?
yes
id
04b30606-3294-4d05-8777-fb56c349b145
date added to LUP
2017-08-21 15:26:21
date last changed
2018-07-29 04:29:03
@article{04b30606-3294-4d05-8777-fb56c349b145,
  abstract     = {<p>Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes. Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNPstroke associations were derived from METASTROKE and the Stroke Genetics Network (n 5 18,476 ischemic stroke cases and 37,296 controls). Results: Conventional MR analysis showed associations between genetically predicted T2D and large artery stroke (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.16-1.40, p 5 3.3 3 1027) and small vessel stroke (OR 1.21, 95% CI 1.10-1.33, p 5 8.9 3 1025) but not cardioembolic stroke (OR 1.06, 95% CI 0.97-1.15, p 5 0.17). The association of T2D with large artery stroke but not small vessel stroke was consistent in a sensitivity analysis using the weighted median method, and there was no evidence of pleiotropy. Genetically predicted fasting glucose and fasting insulin levels and BMI were not statistically significantly associated with any ischemic stroke subtype.</p>},
  author       = {Larsson, Susanna C. and Scott, Robert A. and Traylor, Matthew and Langenberg, Claudia and Hindy, George and Melander, Olle and Orho-Melander, Marju and Seshadri, Sudha and Wareham, Nicholas J and Markus, Hugh S.},
  issn         = {0028-3878},
  language     = {eng},
  month        = {08},
  number       = {5},
  pages        = {454--460},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes : Mendelian randomization study},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000004173},
  volume       = {89},
  year         = {2017},
}