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Metabolic traits and stroke risk in individuals of African ancestry : mendelian randomization analysis |
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| Author: | Fatumo, Segun1,2,3,4; Karhunen, Ville5,6,7; Chikowore, Tinashe8,9; |
| Organizations: |
1The African Computational genomics (TACG) Research group, Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Entebbe, Uganda 2Department of Non-communicable Disease Epidemiology (NCDE), London School of Hygiene and Tropical Medicine London, United Kingdom 3H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Niger
4MRC Biostatistics Unit, School of Clinical Medicine (S.F., S.B.), University of Cambridge, United Kingdom
5Department of Epidemiology and Biostatistics, Medical School Building, St Mary’s Hospital, Imperial College London, United Kingdom 6Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Finland. 7Research Unit of Mathematical Sciences (V.K.), University of Oulu, Finland 8MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 9Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 10The African Center of Excellence in Bioinformatics of Bamako (ACE-B), University of Sciences, Techniques and Technologies of Bamako, Mali 11H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria 12Harvard Medical School, Boston, MA 13Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom 14Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom 15National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, United Kingdom 16Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 17Perelman School of Medicine, University of Pennsylvania, Philadelphia 18Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia 19Department of Biology; Brody School of Medicine Center for Health Disparities, East Carolina University, Greenville, NC 20Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston 21Center for Life Course Health Research, Faculty of Medicine (V.K., M.-R.J.), University of Oulu, Finland 22Biocenter Oulu (M.-R.J.), University of Oulu, Finland 23Unit of Primary Care, Oulu University Hospital, Finland 24Department of Life Sciences, College of Health and Life Sciences, Brunel University London, United Kingdom 25MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, United Kingdom 26Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George’s, University of London, United Kingdom 27Novo Nordisk Research Centre Oxford, Old Road Campus, United Kingdom |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 0.2 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2021102051700 |
| Language: | English |
| Published: |
Wolters Kluwer,
2021
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| Publish Date: | 2021-10-20 |
| Description: |
AbstractBackground and Purpose: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals. Methods: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3734 cases and 18 317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297 626, T2D N=148 726 cases, and 965 732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34 217 cases and 406 111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy. Results: Higher genetically proxied T2D liability, LDL-C (low-density lipoprotein cholesterol), total cholesterol and lower genetically proxied HDL-C (high-density lipoprotein cholesterol) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2D liability [95% CI], 1.09 [1.07–1.11]; per standard-deviation increase in LDL-C, 1.12 [1.04–1.21]; total cholesterol: 1.23 [1.06–1.43]; HDL-C, 0.93 [0.89–0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals. Conclusions: Our analyses support a causal effect of T2D liability and lipid traits on IS risk in African ancestry individuals, with Mendelian randomization estimates similar to those obtained in European ancestry individuals. see all
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| Series: |
Stroke |
| ISSN: | 0039-2499 |
| ISSN-E: | 1524-4628 |
| ISSN-L: | 0039-2499 |
| Volume: | 52 |
| Issue: | 8 |
| Pages: | 2680 - 2684 |
| DOI: | 10.1161/STROKEAHA.121.034747 |
| OADOI: | https://oadoi.org/10.1161/STROKEAHA.121.034747 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3142 Public health care science, environmental and occupational health |
| Subjects: | |
| Funding: |
Dr Fatumo is funded by the Wellcome International Intermediate fellowship (220740/Z/20/Z) at the MRC/UVRI and LSHTM. Dr Gill is supported by the Wellcome 4i Program (203928/Z/16/Z) and by a National Institute for Health Research Clinical Lectureship (CL-2020-16-001) at St. George’s, University of London. Drs Karhunen and Gill are supported by British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College London. Dr Chikowore is an international training fellow supported by the Wellcome Trust grant (214205/Z/18/Z). B. Udosen and M. Nakabuye are supported by the Wellcome Trust. M. Nakabuye and S.F. received support from the Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII). MUII is supported through The Developing Excellence in Leadership, Training and Science (DELTAS) Africa Initiative (grant 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107743) and the UK government. M. Nakabuye acknowledges the support of Makerere University Non-Communicable Diseases (MacNCD). This research is made possible by the MakNCD Research Training Program: National Institutes of Health (NIH) 1D43TW011401-01 through the Fogarty International Center (FIC). CE, B. Udosen, and Dr Fatumo acknowledge H3Africa Bioinformatics Network (H3ABioNet) Node, National Biotechnology Development Agency (NABDA), and the Center for Genomics Research and Innovation (CGRI) Abuja, Nigeria. Dr Damrauer was supported by the Department of Veterans Affairs Office of Research and Development (IK2-CX001780). Dr Mason is funded by the EC-Innovative Medicines Initiative (BigData@Heart). Dr Burgess is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z). This research was funded by UK Research and Innovation (UKRI) Medical Research Council (MC_UU_00002/7) and supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). |
| Copyright information: |
© 2021 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the
terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
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https://creativecommons.org/licenses/by/4.0/ |