@article{ac1925b9fbbe4cebb6921dfa4dbfc904,
title = "A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies",
abstract = "Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 TOPMed samples. We also analyze five non-lipid TOPMed traits.",
author = "{NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium} and {TOPMed Lipids Working Group} and Zilin Li and Xihao Li and Hufeng Zhou and Gaynor, {Sheila M.} and Selvaraj, {Margaret Sunitha} and Theodore Arapoglou and Corbin Quick and Yaowu Liu and Han Chen and Ryan Sun and Rounak Dey and Arnett, {Donna K.} and Auer, {Paul L.} and Bielak, {Lawrence F.} and Bis, {Joshua C.} and Blackwell, {Thomas W.} and John Blangero and Eric Boerwinkle and Bowden, {Donald W.} and Brody, {Jennifer A.} and Cade, {Brian E.} and Conomos, {Matthew P.} and Adolfo Correa and Cupples, {L. Adrienne} and Curran, {Joanne E.} and {de Vries}, {Paul S.} and Ravindranath Duggirala and Nora Franceschini and Freedman, {Barry I.} and G{\"o}ring, {Harald H.H.} and Xiuqing Guo and Kalyani, {Rita R.} and Charles Kooperberg and Kral, {Brian G.} and Lange, {Leslie A.} and Lin, {Bridget M.} and Ani Manichaikul and Manning, {Alisa K.} and Martin, {Lisa W.} and Mathias, {Rasika A.} and Meigs, {James B.} and Mitchell, {Braxton D.} and Montasser, {May E.} and Morrison, {Alanna C.} and Take Naseri and O{\textquoteright}Connell, {Jeffrey R.} and Palmer, {Nicholette D.} and Peyser, {Patricia A.} and Psaty, {Bruce M.} and {de Andrade}, Mariza",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
doi = "10.1038/s41592-022-01640-x",
language = "English (US)",
journal = "Nature Methods",
issn = "1548-7091",
publisher = "Nature Publishing Group",
}