Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.
Adolescent
Adult
Asian People
/ genetics
Atherosclerosis
/ blood
Carotid Intima-Media Thickness
Coronary Disease
/ genetics
Diabetes Mellitus, Type 2
/ genetics
Diabetic Cardiomyopathies
/ blood
Dyslipidemias
/ blood
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Lipids
/ blood
Multifactorial Inheritance
/ genetics
Risk Factors
Diabetes cardiovascular complications
East Asians
Lipid traits
Polygenic risk scores
Subclinical atherosclerosis
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
19 02 2021
19 02 2021
Historique:
received:
17
06
2020
accepted:
12
01
2021
entrez:
20
2
2021
pubmed:
21
2
2021
medline:
21
1
2022
Statut:
epublish
Résumé
The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients. Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10 The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.
Sections du résumé
BACKGROUND
The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.
METHODS
We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients.
RESULTS
Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10
CONCLUSIONS
The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.
Identifiants
pubmed: 33608049
doi: 10.1186/s13073-021-00831-z
pii: 10.1186/s13073-021-00831-z
pmc: PMC7893928
doi:
Substances chimiques
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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