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dc.contributor.authorNomura, Akihiro
dc.contributor.authorWon, Hong-Hee
dc.contributor.authorKhera, Amit V.
dc.contributor.authorTakeuchi, Fumihiko
dc.contributor.authorIto, Kaoru
dc.contributor.authorMcCarthy, Shane
dc.contributor.authorEmdin, Connor A.
dc.contributor.authorKlarin, Derek
dc.contributor.authorNatarajan, Pradeep
dc.contributor.authorGupta, Namrata
dc.contributor.authorPeloso, Gina M.
dc.contributor.authorBorecki, Ingrid B.
dc.contributor.authorTeslovich, Tanya M.
dc.contributor.authorAsselta, Rosanna
dc.contributor.authorDuga, Stefano
dc.contributor.authorMerlini, Piera A.
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorKessler, Thorsten
dc.contributor.authorWilson, James G.
dc.contributor.authorBown, Matthew J.
dc.contributor.authorHall, Alistair S.
dc.contributor.authorBraund, Peter S.
dc.contributor.authorCarey, David J.
dc.contributor.authorKirchner, H. Lester
dc.contributor.authorLeader, Joseph B.
dc.contributor.authorLavage, Daniel R.
dc.contributor.authorManus, J. Neil
dc.contributor.authorHartze, Dustin N.
dc.contributor.authorSamani, Nilesh J.
dc.contributor.authorSchunkert, Heribert
dc.contributor.authorMarrugat, Jaume
dc.contributor.authorElosua, Roberto
dc.contributor.authorMcPherson, Ruth
dc.contributor.authorFarrall, Martin
dc.contributor.authorWatkins, Hugh
dc.contributor.authorJuang, Jyh-Ming J.
dc.contributor.authorHsiung, Chao A.
dc.contributor.authorLin, Shih-Yi
dc.contributor.authorWang, Jun-Sing
dc.contributor.authorTada, Hayato
dc.contributor.authorKawashiri, Masa-aki
dc.contributor.authorInazu, Akihiro
dc.contributor.authorYamagishi, Masakazu
dc.contributor.authorKatsuya, Tomohiro
dc.contributor.authorNakashima, Eitaro
dc.contributor.authorNakatochi, Masahiro
dc.contributor.authorYamamoto, Ken
dc.contributor.authorYokota, Mitsuhiro
dc.contributor.authorMomozawa, Yukihide
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRader, Daniel J.
dc.contributor.authorDanesh, John
dc.contributor.authorArdissino, Diego
dc.contributor.authorGabriel, Stacey
dc.contributor.authorWiller, Cristen J.
dc.contributor.authorAbecasis, Goncalo R.
dc.contributor.authorSaleheen, Danish
dc.contributor.authorKubo, Michiaki
dc.contributor.authorKato, Norihiro
dc.contributor.authorIda Chen, Yii-Der
dc.contributor.authorDewey, Frederick E.
dc.contributor.authorKathiresan, Sekar
dc.contributor.authorZekavat, Seyedeh M.
dc.contributor.authorMurray, Michael F
dc.contributor.authorLander, Eric Steven
dc.date.accessioned2018-06-28T17:47:06Z
dc.date.available2018-06-28T17:47:06Z
dc.date.issued2017-05
dc.date.submitted2017-04
dc.identifier.issn0009-7330
dc.identifier.issn1524-4571
dc.identifier.urihttp://hdl.handle.net/1721.1/116679
dc.description.abstractRationale: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. Objective: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. Methods and Results: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). Conclusions: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD.en_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1161/CIRCRESAHA.117.311145en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleProtein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart DiseaseNovelty and Significanceen_US
dc.typeArticleen_US
dc.identifier.citationNomura, Akihiro et al. “Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease Novelty and Significance.” Circulation Research 121, 1 (May 2017): 81–88 © 2017 American Heart Association, Incen_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorZekavat, Seyedeh M.
dc.contributor.mitauthorMurray, Michael F
dc.contributor.mitauthorLander, Eric Steven
dc.relation.journalCirculation Researchen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-06-28T13:04:05Z
dspace.orderedauthorsNomura, Akihiro; Won, Hong-Hee; Khera, Amit V.; Takeuchi, Fumihiko; Ito, Kaoru; McCarthy, Shane; Emdin, Connor A.; Klarin, Derek; Natarajan, Pradeep; Zekavat, Seyedeh M.; Gupta, Namrata; Peloso, Gina M.; Borecki, Ingrid B.; Teslovich, Tanya M.; Asselta, Rosanna; Duga, Stefano; Merlini, Piera A.; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Carey, David J.; Murray, Michael F.; Kirchner, H. Lester; Leader, Joseph B.; Lavage, Daniel R.; Manus, J. Neil; Hartze, Dustin N.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Juang, Jyh-Ming J.; Hsiung, Chao A.; Lin, Shih-Yi; Wang, Jun-Sing; Tada, Hayato; Kawashiri, Masa-aki; Inazu, Akihiro; Yamagishi, Masakazu; Katsuya, Tomohiro; Nakashima, Eitaro; Nakatochi, Masahiro; Yamamoto, Ken; Yokota, Mitsuhiro; Momozawa, Yukihide; Rotter, Jerome I.; Lander, Eric S.; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Willer, Cristen J.; Abecasis, Goncalo R.; Saleheen, Danish; Kubo, Michiaki; Kato, Norihiro; Ida Chen, Yii-Der; Dewey, Frederick E.; Kathiresan, Sekaren_US
dspace.embargo.termsNen_US
mit.licenseOPEN_ACCESS_POLICYen_US


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