ArticlemedRxiv : the preprint server for health sciences2024
Prioritizing protein targets for dyslipidaemia and cardiovascular diseases using Mendelian randomization in South Asians.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
South Asians are at higher risk of dyslipidaemia-a modifiable risk factor for cardiovascular diseases (CVDs). We aimed to identify protein targets for dyslipidaemia and CVDs in this population. We used a two-sample Mendelian randomization (MR) approach, supplemented with MR-Egger, weighted median, colocalization, and generalized MR (GMR), to evaluate the effect of 2,800 plasma proteins on high/low/non-high-density lipoprotein cholesterol (HDL-C/LDL-C/nonHDL-C), total cholesterol, and triglycerides. Observational analyses were conducted on MR findings with strong colocalization (posterior probability≥ 80%) and GMR findings. Univariate MR assessed lipid-associated proteins' effect on CVDs. Finally, we compared the potential causal effects of plasma proteins on lipids in South Asians with those in Europeans to study heterogeneity in the MR effects. We identified 29 genetically proxied proteins potentially causal to at least one lipid measure, 12 of which showed strong colocalization and GMR evidence, including ANGPTL3 and PCSK9. Notably, PCSK9 demonstrated a stronger association with LDL-C in European compared to South Asian (β
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