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Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.
Tuesday,2018-01-16 18:16 America/Los_Angeles — ecterry
| Title | Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Holzinger, ER, Verma, SS, Moore, CB, Hall, M, De, R, Gilbert-Diamond, D, Lanktree, MB, Pankratz, N, Amuzu, A, Burt, A, Dale, C, Dudek, S, Furlong, CE, Gaunt, TR, Kim, DSeung, Riess, H, Sivapalaratnam, S, Tragante, V, van Iperen, EPA, Brautbar, A, Carrell, DS, Crosslin, DR, Jarvik, GP, Kuivaniemi, H, Kullo, IJ, Larson, EB, Rasmussen-Torvik, LJ, Tromp, G, Baumert, J, Cruickshanks, KJ, Farrall, M, Hingorani, AD, Hovingh, GK, Kleber, ME, Klein, BE, Klein, R, Koenig, W, Lange, LA, Mӓrz, W, North, KE, N Onland-Moret, C, Reiner, AP, Talmud, PJ, van der Schouw, YT, Wilson, JG, Kivimaki, M, Kumari, M, Moore, JH, Drenos, F, Asselbergs, FW, Keating, BJ, Ritchie, MD |
| Journal | BioData Min |
| Volume | 10 |
| Pagination | 25 |
| Date Published | 2017 |
| ISSN | 1756-0381 |
| Abstract | <p><b>BACKGROUND: </b>The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG).</p><p><b>RESULTS: </b>Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing.</p><p><b>CONCLUSIONS: </b>These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.</p> |
| DOI | 10.1186/s13040-017-0145-5 |
| Alternate Journal | BioData Min |
| PubMed ID | 28770004 |
| PubMed Central ID | PMC5525436 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States U01 HG006385 / HG / NHGRI NIH HHS / United States Z01 HG000153 / HG / NHGRI NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States U01 HG006375 / HG / NHGRI NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States U01 HG004438 / HG / NHGRI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01 HL036310 / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U10 EY006594 / EY / NEI NIH HHS / United States Z01 HG200327 / HG / NHGRI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States U01 HG006382 / HG / NHGRI NIH HHS / United States R01 HL095603 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R37 AG011099 / AG / NIA NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States R01 AG021917 / AG / NIA NIH HHS / United States U01 HG004603 / HG / NHGRI NIH HHS / United States U01 HG004424 / HG / NHGRI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01 HG004609 / HG / NHGRI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States U01 HG006389 / HG / NHGRI NIH HHS / United States R37 AG013196 / AG / NIA NIH HHS / United States U01 HG004599 / HG / NHGRI NIH HHS / United States HHSN268201300027C / HL / NHLBI NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States HHSN268201300028C / HL / NHLBI NIH HHS / United States R01 HL067406 / HL / NHLBI NIH HHS / United States R01 AG032136 / AG / NIA NIH HHS / United States U01 HG006380 / HG / NHGRI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States R01 LM010098 / LM / NLM NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States U01 HG006388 / HG / NHGRI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States R01 LM009012 / LM / NLM NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States U01 HG006378 / HG / NHGRI NIH HHS / United States R01 AG013196 / AG / NIA NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States U01 HG004610 / HG / NHGRI NIH HHS / United States U01 HG006379 / HG / NHGRI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States HHSN268201300029C / HL / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States U01 HG004608 / HG / NHGRI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States |
ePub date:
17/07