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A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

by Howard, Barbara V.
Citation: American Journal of Human Genetics. 2018 Feb 13.Journal: American journal of human genetics.Published: 2018ISSN: 0002-9297.Full author list: Sung YJ; Winkler TW; de Las Fuentes L; Bentley AR; Brown MR; Kraja AT; Schwander K; Ntalla I; Guo X; Franceschini N; Lu Y; Cheng CY; Sim X; Vojinovic D; Marten J; Musani SK; Li C; Feitosa MF; Kilpelainen TO; Richard MA; Noordam R; Aslibekyan S; Aschard H; Bartz TM; Dorajoo R; Liu Y; Manning AK; Rankinen T; Smith AV; Tajuddin SM; Tayo BO; Warren HR; Zhao W; Zhou Y; Matoba N; Sofer T; Alver M; Amini M; Boissel M; Chai JF; Chen X; Divers J; Gandin I; Gao C; Giulianini F; Goel A; Harris SE; Hartwig FP; Horimoto ARVR; Hsu FC; Jackson AU; Kahonen M; Kasturiratne A; Kuhnel B; Leander K; Lee WJ; Lin KH; 'an Luan J; McKenzie CA; Meian H; Nelson CP; Rauramaa R; Schupf N; Scott RA; Sheu WHH; Stancakova A; Takeuchi F; van der Most PJ; Varga TV; Wang H; Wang Y; Ware EB; Weiss S; Wen W; Yanek LR; Zhang W; Zhao JH; Afaq S; Alfred T; Amin N; Arking D; Aung T; Barr RG; Bielak LF; Boerwinkle E; Bottinger EP; Braund PS; Brody JA; Broeckel U; Cabrera CP; Cade B; Caizheng Y; Campbell A; Canouil M; Chakravarti A; CHARGE Neurology Working Group; Chauhan G; Christensen K; Cocca M; COGENT-Kidney Consortium; Collins FS; Connell JM; de Mutsert R; de Silva HJ; Debette S; Dorr M; Duan Q; Eaton CB; Ehret G; Evangelou E; Faul JD; Fisher VA; Forouhi NG; Franco OH; Friedlander Y; Gao H; GIANT Consortium; Gigante B; Graff M; Gu CC; Gu D; Gupta P; Hagenaars SP; Harris TB; He J; Heikkinen S; Heng CK; Hirata M; Hofman A; Howard BV; Hunt S; Irvin MR; Jia Y; Joehanes R; Justice AE; Katsuya T; Kaufman J; Kerrison ND; Khor CC; Koh WP; Koistinen HA; Komulainen P; Kooperberg C; Krieger JE; Kubo M; Kuusisto J; Langefeld CD; Langenberg C; Launer LJ; Lehne B; Lewis CE; Li Y; Lifelines Cohort Study; Lim SH; Lin S; Liu CT; Liu J; Liu J; Liu K; Liu Y; Loh M; Lohman KK; Long J; Louie T; Magi R; Mahajan A; Meitinger T; Metspalu A; Milani L; Momozawa Y; Morris AP; Mosley TH Jr.; Munson P; Murray AD; Nalls MA; Nasri U; Norris JM; North K; Ogunniyi A; Padmanabhan S; Palmas WR; Palmer ND; Pankow JS; Pedersen NL; Peters A; Peyser PA; Polasek O; Raitakari OT; Renstrom F; Rice TK; Ridker PM; Robino A; Robinson JG; Rose LM; Rudan I; Sabanayagam C; Salako BL; Sandow K; Schmidt CO; Schreiner PJ; Scott WR; Seshadri S; Sever P; Sitlani CM; Smith JA; Snieder H; Starr JM; Strauch K; Tang H; Taylor KD; Teo YY; Tham YC; Uitterlinden AG; Waldenberger M; Wang L; Wang YX; Wei WB; Williams C; Wilson G; Wojczynski MK; Yao J; Yuan JM; Zonderman AB; Becker DM; Boehnke M; Bowden DW; Chambers JC; Chen YI; de Faire U; Deary IJ; Esko T; Farrall M; Forrester T; Franks PW; Freedman BI; Froguel P; Gasparini P; Gieger C; Horta BL; Hung YJ; Jonas JB; Kato N; Kooner JS; Laakso M; Lehtimaki T; Liang KW; Magnusson PKE; Newman AB; Oldehinkel AJ; Pereira AC; Redline S; Rettig R; Samani NJ; Scott J; Shu XO; van der Harst P; Wagenknecht LE; Wareham NJ; Watkins H; Weir DR; Wickremasinghe AR; Wu T; Zheng W; Kamatani Y; Laurie CC; Bouchard C; Cooper RS; Evans MK; Gudnason V; Kardia SLR; Kritchevsky SB; Levy D; O'Connell JR; Psaty BM; van Dam RM; Sims M; Arnett DK; Mook-Kanamori DO; Kelly TN; Fox ER; Hayward C; Fornage M; Rotimi CN; Province MA; van Duijn CM; Tai ES; Wong TY; Loos RJF; Reiner AP; Rotter JI; Zhu X; Bierut LJ; Gauderman WJ; Caulfield MJ; Elliott P; Rice K; Munroe PB; Morrison AC; Cupples LA; Rao DC; Chasman DI.UI/PMID: 29455858.Subject(s): IN PROCESS -- NOT YET INDEXEDInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1016/j.ajhg.2018.01.015 (Click here) Abbreviated citation: Am J Hum Genet. 2018 Feb 13.Local Holdings: Available online from MWHC library: 1949 - present (after 6 months).Abstract: Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ~18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10<sup>-8</sup>) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10<sup>-8</sup>). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).Abstract: Copyright (c) 2018 American Society of Human Genetics. All rights reserved.

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