Ancestral Diversity in Lipoprotein(a) Studies Helps Address Evidence Gaps

Authors

Moa P Lee
Sofia F Dimos
Laura M Raffield
Zhe Wang
Anna F Ballou
Carolina G Downie
Christopher H Arehart
Adolfo Correa
Paul S de Vries
Zhaohui Du
Christopher R Gignoux
Penny Gordon-Larsen
Xiuqing Guo
Jeffrey Haessler
Annie Green Howard
Yao Hu
Helina Kassahun
Shia T Kent
J Antonio G Lopez
Keri L Monda
Kari E North
Ulrike Peters
Michael H Preuss
Stephen S Rich
Shannon L Rhodes
Jie Yao
Rina Yarosh
Michael Y Tsai
Jerome I Rotter
Charles L Kooperberg
Ruth J F Loos
Christie Ballantyne
Christy L Avery
Mariaelisa Graff

Publication Date

8-1-2023

Journal

BMC Open Heart

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 (R

CONCLUSIONS: Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.

Keywords

Biomarkers, Epidemiology, Genetic Association Studies, Genome-Wide Association Study