{"doi":"10.1007/s00125-021-05537-w","title":"Assessing the linear and non-linear association of HbA1c with cardiovascular disease: a Mendelian randomisation study","abstract":null,"journal":"Diabetologia","year":2021,"id":614187,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":8,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1198716,"name":"Shiu Lun Au Yeung","orcid":"0000-0001-6136-1836","position":1,"is_corresponding":false},{"id":517328,"name":"C. Mary Schooling","orcid":"0000-0001-9933-5887","position":2,"is_corresponding":false},{"id":1433031,"name":"Shan Luo","orcid":"0000-0003-3368-9935","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Assessing the linear and non-linear association of HbA1c with cardiovascular disease: a Mendelian randomisation study","abstract":"<h4>Aims/hypothesis</h4>We aimed to evaluate whether genetically predicted HbA<sub>1c</sub> has an effect on the risk of cardiovascular diseases and investigate the shape of the relationship of genetically predicted HbA<sub>1c</sub> with cardiovascular diseases.<h4>Methods</h4>We performed linear univariable, multivariable and non-linear Mendelian randomisation analyses in 373,571 white British participants (mean age 56.9) from the UK Biobank.<h4>Results</h4>In univariable linear Mendelian randomisation analysis, a 1 mmol/mol increase in genetically predicted HbA<sub>1c</sub> was associated with higher risk of coronary artery disease (OR 1.03, 95% CI 1.02, 1.05), stroke (OR 1.02, 95% CI 1.00, 1.05) and hypertension (OR 1.02, 95% CI 1.01, 1.03). Multivariable Mendelian randomisation adjusted for the effect of haemoglobin gave a consistent conclusion for coronary artery disease. The associations with stroke and hypertension were directionally similar but with wider CI overlapping the null. Non-linear Mendelian randomisation indicated that the shape of the effect of genetically predicted HbA<sub>1c</sub> on cardiovascular outcomes was likely linear.<h4>Conclusions/interpretation</h4>The study suggests a detrimental effect of HbA<sub>1c</sub> on coronary artery disease in both men and women, and the effect is via a glycaemic characteristic. The shape of the genetic association of HbA<sub>1c</sub> with these cardiovascular outcomes, in particular coronary artery disease, is likely to be linear.","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":8,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34345974","pmcid":null,"openalex_id":"https://openalex.org/W3189178145","authors":[],"funders":[{"funder_name":"University of Hong Kong","grant_id":"#201409176231","title":null},{"funder_name":"British Heart Foundation","grant_id":"CH/1996001/9454","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_17228","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_QA137853","title":null}],"total_grants":4,"fwci":3.1796,"citation_percentile":0.92678945,"influential_citations":0,"citation_trend":[{"year":2022,"count":6},{"year":2023,"count":4},{"year":2024,"count":11},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://www.springer.com/tdm","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00125-021-05537-w.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s00125-021-05537-w.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00125-021-05537-w/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00125-021-05537-w","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34345974","host_type":"repository"}],"fields_of_study":["Genetic Associations and Epidemiology","Diabetes Treatment and Management","Diabetes, Cardiovascular Risks, and Lipoproteins","Blood Glucose","Cardiovascular Diseases","Coronary Artery Disease","Female","Genome-Wide Association Study","Glycated Hemoglobin","Glycemic Index","Humans","Hypertension","Male","Mendelian Randomization Analysis","Middle Aged","Risk Factors","Stroke"],"mesh_terms":["Blood Glucose","Cardiovascular Diseases","Coronary Artery Disease","Female","Glycated Hemoglobin","Humans","Hypertension","Male","Middle Aged","Risk Factors","Stroke","Glycemic Index","Genome-Wide Association Study","Mendelian Randomization Analysis"],"keywords":["Medicine","Mendelian randomization","Coronary artery disease","Internal medicine","Stroke (engine)","Disease","Cardiology","Mendelian inheritance","Genetics","Genetic variants","Genotype","Biology","Gene","Cardiovascular disease","Hba1c","Linearity","Uk Biobank","Mendelian Randomisation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.24940412.v1","title":"Additional file 1 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.24940412","title":"Additional file 1 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.24941000.v1","title":"Additional file 2 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.24941000","title":"Additional file 2 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26066152.v1","title":"Additional file 1 of Age-specific differences in association of glycosylated hemoglobin levels with the prevalence of cardiovascular diseases among nondiabetics: the National Health and Nutrition Examination Survey 2005–2018","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26066152","title":"Additional file 1 of Age-specific differences in association of glycosylated hemoglobin levels with the prevalence of cardiovascular diseases among nondiabetics: the National Health and Nutrition Examination Survey 2005–2018","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26660518.v1","title":"Additional file 3 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26660518","title":"Additional file 3 of Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013–2014","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T11:22:33.535321Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}