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eSCAN: scan regulatory regions for aggregate association testing using whole-genome sequencing data.
Thursday,2022-07-21 21:46 America/Los_Angeles — ecterry
| Title | eSCAN: scan regulatory regions for aggregate association testing using whole-genome sequencing data. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Yang, Y, Sun, Q, Huang, L, Broome, JG, Correa, A, Reiner, A, Raffield, LM, Yang, Y, Li, Y |
| Corporate/Institutional Authors | NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium |
| Journal | Brief Bioinform |
| Volume | 23 |
| Issue | 1 |
| Date Published | 2022 01 17 |
| ISSN | 1477-4054 |
| Keywords | Genome, Genome-Wide Association Study, Genomics, Regulatory Sequences, Nucleic Acid, Whole Genome Sequencing |
| Abstract | <p>Multiple statistical methods for aggregate association testing have been developed for whole-genome sequencing (WGS) data. Many aggregate variants in a given genomic window and ignore existing knowledge to define test regions, resulting in many identified regions not clearly linked to genes, and thus, limiting biological understanding. Functional information from new technologies (such as Hi-C and its derivatives), which can help link enhancers to their effector genes, can be leveraged to predefine variant sets for aggregate testing in WGS data. Here, we propose the eSCAN (scan the enhancers) method for genome-wide assessment of enhancer regions in sequencing studies, combining the advantages of dynamic window selection in SCANG (SCAN the Genome), a previously developed method, with the advantages of incorporating putative regulatory regions from annotation. eSCAN, by searching in putative enhancers, increases statistical power and aids mechanistic interpretation, as demonstrated by extensive simulation studies. We also apply eSCAN for blood cell traits using NHLBI Trans-Omics for Precision Medicine WGS data. Results from real data analysis show that eSCAN is able to capture more significant signals, and these signals are of shorter length (indicating higher resolution fine-mapping capability) and drive association of larger regions detected by other methods.</p> |
| DOI | 10.1093/bib/bbab497 |
| Alternate Journal | Brief Bioinform |
| PubMed ID | 34882196 |
| PubMed Central ID | PMC8898002 |
| Grant List | HHSN268201100037C / HL / NHLBI NIH HHS / United States HHSN268201800012C / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201600002C / HL / NHLBI NIH HHS / United States HHSN268201800014C / HL / NHLBI NIH HHS / United States HHSN268201600003C / HL / NHLBI NIH HHS / United States HHSN268201600004C / HL / NHLBI NIH HHS / United States HHSN268201800011C / HL / NHLBI NIH HHS / United States HHSN268201800015I / HB / NHLBI NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States HHSN268201600018C / HL / NHLBI NIH HHS / United States R01 GM105785 / GM / NIGMS NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States R01 HL129132 / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States U01 HG011720 / HG / NHGRI NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States HHSN268201500014C / HL / NHLBI NIH HHS / United States KL2 TR002490 / TR / NCATS NIH HHS / United States HHSN268201600001C / HL / NHLBI NIH HHS / United States |
ePub date:
22/01