Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases

Huiling Zhao, Humaria Rasheed, Therese Haugdahl Nøst, Yoonsu Cho, Yi Liu, Laxmi Bhatta, Arjun Bhattacharya, Gibran Hemani, George Davey Smith, Ben Brumpton, Wei Zhou, Benjamin M. Neale, Tom R. Gaunt, Jie Zheng

Cell Genomics · 2022

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Summary

Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans but with limited evidence in other ancestries. Here, we present a multi-ancestry proteome-wide MR analysis based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the putative causal effects of 1,545 proteins on eight diseases in African (32,658) and European (1,219,993) ancestries and identified 45 and 7 protein-disease pairs with MR and genetic colocalization evidence in the two ancestries, respectively. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence in both ancestries and seven pairs with specific effects in the two ancestries separately. Integrating these MR signals with clinical trial evidence, we prioritize

Source type
Peer-reviewed study
DOI
10.1016/j.xgen.2022.100195
Catalogue ID
SNmojad3ph-9dfclm
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