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Article: The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study
Title | The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study |
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Authors | |
Keywords | Arachidonic acid Atherosclerotic cardiovascular disease Mendelian randomization |
Issue Date | 2021 |
Publisher | Elsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com |
Citation | EBioMedicine, 2021, v. 63, p. article no. 103189 How to Cite? |
Abstract | Background:
Arachidonic acid (AA), a major long-chain n-6 polyunsaturated fatty acid in animal foods, has been linked to inflammation, coagulation, and testosterone, which might relate to atherosclerotic cardiovascular diseases (ASCVD). We assessed the associations of genetically predicted plasma phospholipid AA with ASCVD and other CVD overall and by sex using Mendelian randomization (MR).
Methods:
We conducted two-sample MR, applying eight genetic variants, independent of a highly pleiotropic variant (rs174547), strongly (p < 5 × 10−8) predicting AA, primarily to summary statistics of genetic associations with ASCVD, including ischaemic heart disease (IHD), ischaemic stroke, and peripheral artery disease (PAD) from CARDIoGRAMplusC4D 1000 Genomes (60,801 IHD cases, 123,504 controls), MEGASTROKE (34,217 ischaemic stroke cases, 406,111 controls), and Pan-UK Biobank (n=~420,531), and secondarily to genetic associations with other CVD from Pan-UK Biobank, Atrial Fibrillation Consortium, HERMES consortium, and FinnGen. We also assessed sex differences.
Findings:
Genetically predicted AA was associated with ASCVD (odds ratio (OR) per % of total fatty acids increase 1.03, 95% confidence interval (CI) 1.01 to 1.05) and its subtypes IHD (OR 1.03, 95% CI 1.004 to 1.05), ischaemic stroke (OR 1.03, 95% CI 1.004 to 1.06) and possibly PAD (OR 1.08, 95% CI 1.00 to 1.17), possibly more strongly in men than women. AA was also associated with venous thromboembolism (OR 1.12, 95% CI 1.05 to 1.19). A similar pattern was observed when using rs174547 to genetically predict AA.
Interpretation:
Our study suggests positive associations of AA with ASCVD and venous thromboembolism, with possibly stronger associations in men than women.
Funding:
No funding. |
Persistent Identifier | http://hdl.handle.net/10722/305704 |
ISSN | 2023 Impact Factor: 9.7 2023 SCImago Journal Rankings: 3.193 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | ZHANG, T | - |
dc.contributor.author | Zhao, JV | - |
dc.contributor.author | Schooling, CM | - |
dc.date.accessioned | 2021-10-20T10:13:08Z | - |
dc.date.available | 2021-10-20T10:13:08Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | EBioMedicine, 2021, v. 63, p. article no. 103189 | - |
dc.identifier.issn | 2352-3964 | - |
dc.identifier.uri | http://hdl.handle.net/10722/305704 | - |
dc.description.abstract | Background: Arachidonic acid (AA), a major long-chain n-6 polyunsaturated fatty acid in animal foods, has been linked to inflammation, coagulation, and testosterone, which might relate to atherosclerotic cardiovascular diseases (ASCVD). We assessed the associations of genetically predicted plasma phospholipid AA with ASCVD and other CVD overall and by sex using Mendelian randomization (MR). Methods: We conducted two-sample MR, applying eight genetic variants, independent of a highly pleiotropic variant (rs174547), strongly (p < 5 × 10−8) predicting AA, primarily to summary statistics of genetic associations with ASCVD, including ischaemic heart disease (IHD), ischaemic stroke, and peripheral artery disease (PAD) from CARDIoGRAMplusC4D 1000 Genomes (60,801 IHD cases, 123,504 controls), MEGASTROKE (34,217 ischaemic stroke cases, 406,111 controls), and Pan-UK Biobank (n=~420,531), and secondarily to genetic associations with other CVD from Pan-UK Biobank, Atrial Fibrillation Consortium, HERMES consortium, and FinnGen. We also assessed sex differences. Findings: Genetically predicted AA was associated with ASCVD (odds ratio (OR) per % of total fatty acids increase 1.03, 95% confidence interval (CI) 1.01 to 1.05) and its subtypes IHD (OR 1.03, 95% CI 1.004 to 1.05), ischaemic stroke (OR 1.03, 95% CI 1.004 to 1.06) and possibly PAD (OR 1.08, 95% CI 1.00 to 1.17), possibly more strongly in men than women. AA was also associated with venous thromboembolism (OR 1.12, 95% CI 1.05 to 1.19). A similar pattern was observed when using rs174547 to genetically predict AA. Interpretation: Our study suggests positive associations of AA with ASCVD and venous thromboembolism, with possibly stronger associations in men than women. Funding: No funding. | - |
dc.language | eng | - |
dc.publisher | Elsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com | - |
dc.relation.ispartof | EBioMedicine | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Arachidonic acid | - |
dc.subject | Atherosclerotic cardiovascular disease | - |
dc.subject | Mendelian randomization | - |
dc.title | The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study | - |
dc.type | Article | - |
dc.identifier.email | Zhao, JV: janezhao@hku.hk | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.authority | Zhao, JV=rp02336 | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.ebiom.2020.103189 | - |
dc.identifier.pmid | 33418501 | - |
dc.identifier.pmcid | PMC7804604 | - |
dc.identifier.scopus | eid_2-s2.0-85098954754 | - |
dc.identifier.hkuros | 328037 | - |
dc.identifier.volume | 63 | - |
dc.identifier.spage | article no. 103189 | - |
dc.identifier.epage | article no. 103189 | - |
dc.identifier.isi | WOS:000697459100010 | - |
dc.publisher.place | Netherlands | - |