A1 Refereed original research article in a scientific journal

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure




AuthorsSung YJ, de Las Fuentes L, Winkler TW, Chasman DI, Bentley AR, Kraja AT, Ntalla I, Warren HR, Guo X, Schwander K, Manning AK, Brown MR, Aschard H, Feitosa MF, Franceschini N, Lu Y, Cheng CY, Sim X, Vojinovic D, Marten J, Musani SK, Kilpeläinen TO, Richard MA, Aslibekyan S, Bartz TM, Dorajoo R, Li C, Liu Y, Rankinen T, Smith AV, Tajuddin SM, Tayo BO, 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, He M, Horimoto ARVR, Hsu FC, Jackson AU, Kammerer CM, Kasturiratne A, Komulainen P, Kühnel B, Leander K, Lee WJ, Lin KH, Luan J, Lyytikäinen LP, McKenzie CA, Nelson CP, Noordam R, Scott RA, Sheu WHH, Stančáková A, Takeuchi F, van der Most PJ, Varga TV, Waken RJ, Wang H, Wang Y, Ware EB, Weiss S, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Alfred T, Amin N, Arking DE, Aung T, Barr RG, Bielak LF, Boerwinkle E, Bottinger EP, Braund PS, Brody JA, Broeckel U, Cade B, Campbell A, Canouil M, Chakravarti A, Cocca M, Collins FS, Connell JM, de Mutsert R, de Silva HJ, Dörr M, Duan Q, Eaton CB, Ehret G, Evangelou E, Faul JD, Forouhi NG, Franco OH, Friedlander Y, Gao H, Gigante B, Gu CC, Gupta P, Hagenaars SP, Harris TB, He J, Heikkinen S, Heng CK, Hofman A, Howard BV, Hunt SC, Irvin MR, Jia Y, Katsuya T, Kaufman J, Kerrison ND, Khor CC, Koh WP, Koistinen HA, Kooperberg CB, Krieger JE, Kubo M, Kutalik Z, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lee JH, Lehne B, Levy D, Lewis CE, Li Y; Lifelines Cohort Study, Lim SH, Liu CT, Liu J, Liu J, Liu Y, Loh M, Lohman KK, Louie T, Mägi R, Matsuda K, Meitinger T, Metspalu A, Milani L, Momozawa Y, Mosley TH Jr, Nalls MA, Nasri U, O'Connell JR, Ogunniyi A, Palmas WR, Palmer ND, Pankow JS, Pedersen NL, Peters A, Peyser PA, Polasek O, Porteous D, Raitakari OT, Renström 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, Sever P, Sims M, Sitlani CM, Smith BH, 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, Wilson G, Wojczynski MK, Xiang YB, Yao J, Yuan JM, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Chen YI, Weir DR, de Faire U, Deary IJ, Esko T, Farrall M, Forrester T, Freedman BI, Froguel P, Gasparini P, Gieger C, Horta BL, Hung YJ, Jonas JB, Kato N, Kooner JS, Laakso M, Lehtimäki T, Liang KW, Magnusson PKE, Oldehinkel AJ, Pereira AC, Perls T, Rauramaa R, Redline S, Rettig R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wareham NJ, Watkins H, Wickremasinghe AR, Wu T, Kamatani Y, Laurie CC, Bouchard C, Cooper RS, Evans MK, Gudnason V, Hixson J, Kardia SLR, Kritchevsky SB, Psaty BM, van Dam RM, Arnett DK, Mook-Kanamori DO, Fornage M, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Loos RJF, Reiner AP, Rotimi CN, Bierut LJ, Zhu X, Cupples LA, Province MA, Rotter JI, Franks PW, Rice K, Elliott P, Caulfield MJ, Gauderman WJ, Munroe PB, Rao DC, Morrison AC

Publication year2019

JournalHuman Molecular Genetics

Volume28

Issue15

First page 2615

Last page2633

Number of pages19

ISSN0964-6906

DOIhttps://doi.org/10.1093/hmg/ddz070

Self-archived copy’s web addresshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644157/


Abstract

Elevated blood pressure (BP), a leading cause of global morbidity and
mortality, is influenced by both genetic and lifestyle factors.
Cigarette smoking is one such lifestyle factor. Across five ancestries,
we performed a genome-wide gene-smoking interaction study of mean
arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals
in stage 1 and follow-up analysis in 480 178 additional individuals in
stage 2. We report here 136 loci significantly associated with MAP
and/or PP. Of these, 61 were previously published through main-effect
analysis of BP traits, 37 were recently reported by us for systolic BP
and/or diastolic BP through gene-smoking interaction analysis and 38
were newly identified (P < 5 × 10-8, false discovery rate < 0.05).
We also identified nine new signals near known loci. Of the 136 loci, 8
showed significant interaction with smoking status. They include CSMD1
previously reported for insulin resistance and BP in the spontaneously
hypertensive rats. Many of the 38 new loci show biologic plausibility
for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate
exchanger expressed in the renal outer medullary collecting duct. AVPR1A
is widely expressed, including in vascular smooth muscle cells, kidney,
myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in
heart failure. TMEM51 was associated with contractile function in
cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis.
Identified only in African ancestry were 30 novel loci. Our findings
highlight the value of multi-ancestry investigations, particularly in
studies of interaction with lifestyle factors, where genomic and
lifestyle differences may contribute to novel findings.



Last updated on 2024-26-11 at 19:06