7 research outputs found
Ancestral Diversity in Lipoprotein(a) Studies Helps Address Evidence Gaps
INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in \u3e1.5 billion individuals worldwide, but studies have prioritised European populations.
METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)\u27s 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
Progression of the load of waterborne and intestinal parasitic diseases in the State of Amazonas
Pesquisa de aglutininas antileptospira em diferentes grupos profissionais na cidade de Londrina, Paraná
De novo mutation of theDHCR7 gene in a fetus with severe Smith–Lemli–Opitz (or RSH) syndrome
Leptospirose humana no municÃpio de Belo Horizonte, Minas Gerais, Brasil: uma abordagem geográfica
Ancestral diversity in lipoprotein(a) studies helps address evidence gaps
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