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Association of TIM-1 (T-Cell Immunoglobulin and Mucin Domain 1) With Incidence of Stroke

Song, Lu ; Sun, Jiangming LU orcid ; Söderholm, Martin LU ; Melander, Olle LU orcid ; Orho-Melander, Marju LU ; Nilsson, Jan LU ; Borné, Yan LU and Engström, Gunnar LU (2020) In Arteriosclerosis, Thrombosis, and Vascular Biology 40(7). p.1777-1786
Abstract

OBJECTIVE: The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke. Approach and Results: Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during... (More)

OBJECTIVE: The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke. Approach and Results: Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during follow-up, of which 338 were ischemic strokes. After risk factor adjustment, TIM-1 was associated with increased incidence of all-cause stroke (hazards ratio for third versus first tertile, 1.44 [95% CI, 1.10-1.87]; P for trend, 0.004), and ischemic stroke (hazards ratio, 1.42 [95% CI, 1.06-1.90]; P for trend, 0.011). Nineteen independent lead SNPs, located in three genomic risk loci showed significant associations with TIM-1 (P<5×10-8). A 2-sample Mendelian Randomization analysis suggested a causal effect of TIM-1 on stroke (β=0.083, P=0.0004) and ischemic stroke (β=0.102, P=7.7×10-5). CONCLUSIONS: Plasma level of TIM-1 is associated with incidence of stroke. The genetic analyses suggest that this could be a causal relationship.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diabetes mellitus, incidence, mendelian randomization analysis, Genome wide association study, stroke, TIM-1, Genetic Predisposition to Disease
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
40
issue
7
pages
10 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85087110462
  • pmid:32460577
ISSN
1524-4636
DOI
10.1161/ATVBAHA.120.314269
language
English
LU publication?
yes
id
91d88f05-e177-40e8-ad30-dfa30a207da8
date added to LUP
2020-07-07 11:07:05
date last changed
2024-05-29 16:21:57
@article{91d88f05-e177-40e8-ad30-dfa30a207da8,
  abstract     = {{<p>OBJECTIVE: The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke. Approach and Results: Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during follow-up, of which 338 were ischemic strokes. After risk factor adjustment, TIM-1 was associated with increased incidence of all-cause stroke (hazards ratio for third versus first tertile, 1.44 [95% CI, 1.10-1.87]; P for trend, 0.004), and ischemic stroke (hazards ratio, 1.42 [95% CI, 1.06-1.90]; P for trend, 0.011). Nineteen independent lead SNPs, located in three genomic risk loci showed significant associations with TIM-1 (P&lt;5×10-8). A 2-sample Mendelian Randomization analysis suggested a causal effect of TIM-1 on stroke (β=0.083, P=0.0004) and ischemic stroke (β=0.102, P=7.7×10-5). CONCLUSIONS: Plasma level of TIM-1 is associated with incidence of stroke. The genetic analyses suggest that this could be a causal relationship.</p>}},
  author       = {{Song, Lu and Sun, Jiangming and Söderholm, Martin and Melander, Olle and Orho-Melander, Marju and Nilsson, Jan and Borné, Yan and Engström, Gunnar}},
  issn         = {{1524-4636}},
  keywords     = {{diabetes mellitus; incidence; mendelian randomization analysis; Genome wide association study; stroke; TIM-1; Genetic Predisposition to Disease}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1777--1786}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
  title        = {{Association of TIM-1 (T-Cell Immunoglobulin and Mucin Domain 1) With Incidence of Stroke}},
  url          = {{http://dx.doi.org/10.1161/ATVBAHA.120.314269}},
  doi          = {{10.1161/ATVBAHA.120.314269}},
  volume       = {{40}},
  year         = {{2020}},
}