Association of TIM-1 (T-Cell Immunoglobulin and Mucin Domain 1) With Incidence of Stroke
(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
- Song, Lu ; Sun, Jiangming LU ; Söderholm, Martin LU ; Melander, Olle LU ; Orho-Melander, Marju LU ; Nilsson, Jan LU ; Borné, Yan LU and Engström, Gunnar LU
- organization
-
- Cardiovascular Research - Translational Studies (research group)
- Cardiovascular Research - Epidemiology (research group)
- Cardiovascular Research - Hypertension (research group)
- EpiHealth: Epidemiology for Health
- EXODIAB: Excellence of Diabetes Research in Sweden
- Diabetes - Cardiovascular Disease (research group)
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- publishing date
- 2020
- 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<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}}, }