Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.
Open Heart
; 10(2)2023 08.
Article
in En
| MEDLINE
| ID: mdl-37648373
ABSTRACT
INTRODUCTION:
The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.METHODS:
Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.RESULTS:
Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R2=15% in East Asians) to high (R2=50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10-6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects.CONCLUSIONS:
Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
/
Myocardial Ischemia
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Open Heart
Year:
2023
Document type:
Article
Affiliation country: