作者
Xuan Wang, Molei Liu, Isabelle-Emmanuella Nogues, Tony Chen, Xin Xiong, Clara-Lea Bonzel, Harrison Zhang, Chuan Hong, Yin Xia, Kumar Dahal, Lauren Costa, Jing Cui, VA Million Veteran Program MVP Program Office Muralidhar Sumitra 12 Moser Jennifer 12 Deen Jennifer E. 12, MVP Executive Committee Tsao Philip S. 13 Muralidhar Sumitra 12 Gaziano J. Michael 14 Hauser Elizabeth 15 Kilbourne Amy 16 Luoh Shiuh-Wen 17 Matheny Michael 18 Oslin Dave 19, MVP Co-Principal Investigators Gaziano J. Michael 14 Tsao Philip S. 13, Themistocles L Assimes, Adriana Hung, Henry Kranzler, Samuel Aguayo, Sunil Ahuja, Kathrina Alexander, Xiao M Androulakis, Prakash Balasubramanian, Zuhair Ballas, Jean Beckham, Sujata Bhushan, Edward Boyko, David Cohen, Louis Dellitalia, L Christine Faulk, Joseph Fayad, Daryl Fujii, Saib Gappy, Frank Gesek, Jennifer Greco, Michael Godschalk, Todd W Gress, Samir Gupta, Salvador Gutierrez, John Harley, Kimberly Hammer, Mark Hamner, Adriana Hung, Robin Hurley, Pran Iruvanti, Frank Jacono, Darshana Jhala, Scott Kinlay, Jon Klein, Michael Landry, Peter Liang, Suthat Liangpunsakul, Jack Lichy, C Scott Mahan, Ronnie Marrache, Stephen Mastorides, Elisabeth Mates, Kristin Mattocks, Paul Meyer, Jonathan Moorman, Timothy Morgan, Maureen Murdoch, James Norton, Olaoluwa Okusaga, Kris Ann Oursler, Ana Palacio, Samuel Poon, Emily Potter, Michael Rauchman, Richard Servatius, Satish Sharma, River Smith, Peruvemba Sriram, Patrick Strollo Jr, Neeraj Tandon, Philip Tsao, Gerardo Villareal, Agnes Wallbom, Jessica Walsh, John Wells, Jeffrey Whittle, Mary Whooley, Allison E Williams, Peter Wilson, Junzhe Xu, Shing Shing Yeh
发表日期
2024/4/5
期刊
Scientific reports
卷号
14
期号
1
页码范围
8021
出版商
Nature Publishing Group UK
简介
The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype–phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10–3), and higher …
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X Wang, M Liu, IE Nogues, T Chen, X Xiong, CL Bonzel… - Scientific reports, 2024