Associations of Genetically Predicted Lp(a) (Lipoprotein [a]) Levels With Cardiovascular Traits in Individuals of European and African Ancestry.
Mendelian randomization analysis
atherosclerosis
cardiovascular disease
heart failure
lipoprotein
Journal
Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
pubmed:
21
7
2021
medline:
12
2
2022
entrez:
20
7
2021
Statut:
ppublish
Résumé
Lp(a) (lipoprotein [a]) levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with (1) atherosclerotic cardiovascular disease subtypes: coronary heart disease, cerebrovascular disease, peripheral artery disease, and abdominal aortic aneurysm and (2) nonatherosclerotic cardiovascular disease phenotypes, stratified by ancestry. We performed (1) Mendelian randomization analyses for previously reported cardiovascular associations and (2) Mendelian randomization-phenome-wide association analyses for novel associations. Analyses were stratified by ancestry in electronic Medical Records and Genomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804 507 EA and 103 580 AA participants. In Mendelian randomization analyses using the combined cohort, a 1-SD genetic increase in Lp(a) level was associated with atherosclerotic cardiovascular disease subtypes in EA-odds ratio and 95% CI for coronary heart disease 1.28 (1.16-1.41); cerebrovascular disease 1.14 (1.07-1.21); peripheral artery disease 1.22 (1.11-1.34); abdominal aortic aneurysm 1.28 (1.17-1.40); in AA, the effect estimate was lower than in EA and nonsignificant for coronary heart disease 1.11 (0.99-1.24) and cerebrovascular disease 1.06 (0.99-1.14) but similar for peripheral artery disease 1.16 (1.01-1.33) and abdominal aortic aneurysm 1.34 (1.11-1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34 (1.10-1.62), mitral valve disorders 1.18 (1.09-1.27), congestive heart failure 1.12 (1.05-1.19), and chronic kidney disease 1.07 (1.01-1.14). In AA, no significant associations were noted for aortic valve disorders 1.08 (0.94-1.25), mitral valve disorders 1.02 (0.89-1.16), congestive heart failure 1.02 (0.95-1.10), or chronic kidney disease 1.05 (0.99-1.12). Mendelian randomization-phenome-wide association analyses identified novel associations in EA with arterial thromboembolic disease, nonaortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension. Many cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with atherosclerotic cardiovascular disease in four major arterial beds in EA but only with peripheral artery disease and abdominal aortic aneurysm in AA. Additionally, novel cardiovascular associations were detected in EA.
Sections du résumé
BACKGROUND
Lp(a) (lipoprotein [a]) levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with (1) atherosclerotic cardiovascular disease subtypes: coronary heart disease, cerebrovascular disease, peripheral artery disease, and abdominal aortic aneurysm and (2) nonatherosclerotic cardiovascular disease phenotypes, stratified by ancestry.
METHODS
We performed (1) Mendelian randomization analyses for previously reported cardiovascular associations and (2) Mendelian randomization-phenome-wide association analyses for novel associations. Analyses were stratified by ancestry in electronic Medical Records and Genomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804 507 EA and 103 580 AA participants.
RESULTS
In Mendelian randomization analyses using the combined cohort, a 1-SD genetic increase in Lp(a) level was associated with atherosclerotic cardiovascular disease subtypes in EA-odds ratio and 95% CI for coronary heart disease 1.28 (1.16-1.41); cerebrovascular disease 1.14 (1.07-1.21); peripheral artery disease 1.22 (1.11-1.34); abdominal aortic aneurysm 1.28 (1.17-1.40); in AA, the effect estimate was lower than in EA and nonsignificant for coronary heart disease 1.11 (0.99-1.24) and cerebrovascular disease 1.06 (0.99-1.14) but similar for peripheral artery disease 1.16 (1.01-1.33) and abdominal aortic aneurysm 1.34 (1.11-1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34 (1.10-1.62), mitral valve disorders 1.18 (1.09-1.27), congestive heart failure 1.12 (1.05-1.19), and chronic kidney disease 1.07 (1.01-1.14). In AA, no significant associations were noted for aortic valve disorders 1.08 (0.94-1.25), mitral valve disorders 1.02 (0.89-1.16), congestive heart failure 1.02 (0.95-1.10), or chronic kidney disease 1.05 (0.99-1.12). Mendelian randomization-phenome-wide association analyses identified novel associations in EA with arterial thromboembolic disease, nonaortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension.
CONCLUSIONS
Many cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with atherosclerotic cardiovascular disease in four major arterial beds in EA but only with peripheral artery disease and abdominal aortic aneurysm in AA. Additionally, novel cardiovascular associations were detected in EA.
Identifiants
pubmed: 34282949
doi: 10.1161/CIRCGEN.120.003354
pmc: PMC8634549
mid: NIHMS1724683
doi:
Substances chimiques
LPA protein, human
0
Lipoprotein(a)
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e003354Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG006385
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006382
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004603
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004424
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004599
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006380
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004610
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006379
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004608
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006375
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL137010
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004609
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006389
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006388
Pays : United States
Organisme : BLRD VA
ID : I01 BX003362
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008680
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006378
Pays : United States
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