Rare variant associations with plasma protein levels in the UK Biobank

Ryan S. Dhindsa, Oliver S. Burren, Benjamin B. Sun, Bram P. Prins, Dorota Matelska, Eleanor Wheeler, Jonathan Mitchell, Erin Oerton, Ventzislava A. Hristova, Katherine R. Smith, Keren Carss, Sebastian Wasilewski, Andrew R. Harper, Dirk S. Paul, Margarete A. Fabre, Heiko Runz, Coralie Viollet, Benjamin Challis, Adam Platt, AstraZeneca Genomics Initiative, Rasmus Ågren, Lauren Anderson-Dring, Santosh S. Atanur, David H. Baker, Carl Barrett, Maria G. Belvisi, Mohammad Bohlooly‐Y, Lisa Buvall, Niedzica Camacho, Lisa H. Cazares, Sophia Cameron‐Christie, Morris Chen, E. Suzanne Cohen, Regina Fritsche Danielson, Shikta Das, Andrew Davis, Sri Vishnu Vardhan Deevi, Wei Ding, Brian Dougherty, Zammy Fairhurst-Hunter, Manik Garg, Benjamin Georgi, Carmen Guerrero Rangel, Carolina Haefliger, Mårten Hammar, Richard N. Hanna, Pernille Hansen, Jennifer Harrow, Ian Henry, Sonja Hess, Ben Hollis, Fengyuan Hu, Xiao Jiang, Kousik Kundu, Zhongwu Lai, Mark Lal, Glenda Lassi, Yupu Liang, Margarida Lopes, Kieren Lythgow, Stewart MacArthur, Meeta Maisuria-Armer, Ruth March, Carla Martins, Karyn Mégy, Robert Menzies, Erik Michaëlsson, Fiona K. Middleton, Bill Mowrey, Daniel Muthas, Abhishek Nag, Sean M. O’Dell, Yoichiro Ohne, Henric Olsson, Amanda O’Neill, Kristoffer Ostridge, Benjamin Pullman, William Rae, Arwa Bin Raies, Anna Reznichenko, Xavier Romero Ros, Maria Ryaboshapkina, Hitesh J. Sanganee, Ben S. Sidders, Mike Snowden, Stasa Stankovic, Helen Stevens, Ioanna Tachmazidou, Haeyam Taiy, Lifeng Tian, Christina Underwood, Anna Walentinsson, Qing‐Dong Wang, Ahmet Zehir, Zoe Zou, Dimitrios Vitsios, Euan A. Ashley, Christopher D. Whelan, Menelas N. Pangalos, Quanli Wang

Nature · 2023

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Summary

. We then looked at aggregate signals using gene-level collapsing analysis, which revealed 1,962 gene-protein associations. Of the 691 gene-level signals from protein-truncating variants, 99.4% were associated with decreased protein levels. STAB1 and STAB2, encoding scavenger receptors involved in plasma protein clearance, emerged as pleiotropic loci, with 77 and 41 protein associations, respectively. We demonstrate the utility of our publicly accessible resource through several applications. These include detailing an allelic series in NLRC4, identifying potential biomarkers for a fatty liver disease-associated variant in HSD17B13 and bolstering phenome-wide association studies by integrating protein quantitative trait loci with protein-truncating variants in collapsing analyses. Finally,

Source type: Peer-reviewed study
DOI: 10.1038/s41586-023-06547-x
Catalogue ID: SNmoj1y2gk-esw5t5

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