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Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage

BACKGROUND: The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH. METHODS AND RESULTS: We conducted a 2 sample Mendelian Randomiz...

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Autores principales: Szejko, Natalia, Acosta, Julian N., Both, Cameron P., Leasure, Audrey, Matouk, Charles, Sansing, Lauren, Gill, Thomas M., Hongyu, Zhao, Sheth, Kevin, Falcone, Guido J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333362/
https://www.ncbi.nlm.nih.gov/pubmed/35730641
http://dx.doi.org/10.1161/JAHA.121.024141
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author Szejko, Natalia
Acosta, Julian N.
Both, Cameron P.
Leasure, Audrey
Matouk, Charles
Sansing, Lauren
Gill, Thomas M.
Hongyu, Zhao
Sheth, Kevin
Falcone, Guido J.
author_facet Szejko, Natalia
Acosta, Julian N.
Both, Cameron P.
Leasure, Audrey
Matouk, Charles
Sansing, Lauren
Gill, Thomas M.
Hongyu, Zhao
Sheth, Kevin
Falcone, Guido J.
author_sort Szejko, Natalia
collection PubMed
description BACKGROUND: The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH. METHODS AND RESULTS: We conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43]; P=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38]; P=0.17). CONCLUSIONS: Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.
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spelling pubmed-93333622022-07-30 Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage Szejko, Natalia Acosta, Julian N. Both, Cameron P. Leasure, Audrey Matouk, Charles Sansing, Lauren Gill, Thomas M. Hongyu, Zhao Sheth, Kevin Falcone, Guido J. J Am Heart Assoc Brief Communication BACKGROUND: The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH. METHODS AND RESULTS: We conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43]; P=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38]; P=0.17). CONCLUSIONS: Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH. John Wiley and Sons Inc. 2022-06-22 /pmc/articles/PMC9333362/ /pubmed/35730641 http://dx.doi.org/10.1161/JAHA.121.024141 Text en © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communication
Szejko, Natalia
Acosta, Julian N.
Both, Cameron P.
Leasure, Audrey
Matouk, Charles
Sansing, Lauren
Gill, Thomas M.
Hongyu, Zhao
Sheth, Kevin
Falcone, Guido J.
Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title_full Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title_fullStr Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title_full_unstemmed Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title_short Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
title_sort genetically‐proxied levels of vitamin d and risk of intracerebral hemorrhage
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333362/
https://www.ncbi.nlm.nih.gov/pubmed/35730641
http://dx.doi.org/10.1161/JAHA.121.024141
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