Dataset Information

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.

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.

SUBMITTER: Lee MP

PROVIDER: S-EPMC10471864 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.

Lee Moa P MP Dimos Sofia F SF Raffield Laura M LM Wang Zhe Z Ballou Anna F AF Downie Carolina G CG Arehart Christopher H CH Correa Adolfo A de Vries Paul S PS Du Zhaohui Z Gignoux Christopher R CR Gordon-Larsen Penny P Guo Xiuqing X Haessler Jeffrey J Howard Annie Green AG Hu Yao Y Kassahun Helina H Kent Shia T ST Lopez J Antonio G JAG Monda Keri L KL North Kari E KE Peters Ulrike U Preuss Michael H MH Rich Stephen S SS Rhodes Shannon L SL Yao Jie J Yarosh Rina R Tsai Michael Y MY Rotter Jerome I JI Kooperberg Charles L CL Loos Ruth J F RJF Ballantyne Christie C Avery Christy L CL Graff Mariaelisa M

Open heart 20230801 2

<h4>Introduction</h4>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.<h4>Methods</h4>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), ...[more]

PMID: 37648373

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Dataset Information

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.

Introduction

Methods

Results

Conclusions

Publications

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.

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