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Identification of putative causal loci in whole-genome sequencing data via knockoff statistics.
Tuesday,2021-07-20 14:43 America/Los_Angeles — ecterry
| Title | Identification of putative causal loci in whole-genome sequencing data via knockoff statistics. |
| Publication Type | Journal Article |
| Year of Publication | 2021 |
| Authors | He, Z, Liu, L, Wang, C, Le Guen, Y, Lee, J, Gogarten, S, Lu, F, Montgomery, S, Tang, H, Silverman, EK, Cho, MH, Greicius, M, Ionita-Laza, I |
| Journal | Nat Commun |
| Volume | 12 |
| Issue | 1 |
| Pagination | 3152 |
| Date Published | 2021 05 25 |
| ISSN | 2041-1723 |
| Keywords | Algorithms, Causality, Computer Simulation, Data Interpretation, Statistical, Datasets as Topic, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Markov Chains, Models, Genetic, Polymorphism, Single Nucleotide, Reproducibility of Results, Whole Genome Sequencing |
| Abstract | <p>The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability, and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here. In applications to whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) and COPDGene samples from NHLBI Trans-Omics for Precision Medicine (TOPMed) Program we show that our method compared with conventional association tests can lead to substantially more discoveries.</p> |
| DOI | 10.1038/s41467-021-22889-4 |
| Alternate Journal | Nat Commun |
| PubMed ID | 34035245 |
| PubMed Central ID | PMC8149672 |
| Grant List | R01 AG023629 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 AG052411 / AG / NIA NIH HHS / United States HHSN268201500001I / HL / NHLBI NIH HHS / United States U01 HL096812 / HL / NHLBI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U01 AG052410 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States R01 MH106910 / MH / NIMH NIH HHS / United States U01 AG049506 / AG / NIA NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States R01 HL089856 / HL / NHLBI NIH HHS / United States U01 AG049508 / AG / NIA NIH HHS / United States R01 AG049607 / AG / NIA NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States HHSN268201500014C / HL / NHLBI NIH HHS / United States U01 AG057659 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 HL089856 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 AG054076 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States U01 HL096902 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U24 AG041689 / AG / NIA NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 AG033040 / AG / NIA NIH HHS / United States U01 HL096899 / HL / NHLBI NIH HHS / United States UF1 AG047133 / AG / NIA NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States U54 AG052427 / AG / NIA NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States R01 AG066206 / AG / NIA NIH HHS / United States U01 HL096814 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States R01 MH095797 / MH / NIMH NIH HHS / United States U01 AG049507 / AG / NIA NIH HHS / United States U54 HG003079 / HG / NHGRI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States |
ePub date:
21/05