PLoS Medicine (Apr 2022)

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries.

  • Andrew B Linden,
  • Robert Clarke,
  • Imen Hammami,
  • Jemma C Hopewell,
  • Yu Guo,
  • William N Whiteley,
  • Kuang Lin,
  • Iain Turnbull,
  • Yiping Chen,
  • Canqing Yu,
  • Jun Lv,
  • Alison Offer,
  • Derrick Bennett,
  • Robin G Walters,
  • Liming Li,
  • Zhengming Chen,
  • Sarah Parish,
  • China Kadoorie Biobank Collaborative Group

DOI
https://doi.org/10.1371/journal.pmed.1003967
Journal volume & issue
Vol. 19, no. 4
p. e1003967

Abstract

Read online

BackgroundTaller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.Methods and findingsHeight-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p ConclusionsThe findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.