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Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

ABSTRACT: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

SUBMITTER: Wain LV 

PROVIDER: S-EPMC3445021 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Wain Louise V LV   Verwoert Germaine C GC   O'Reilly Paul F PF   Shi Gang G   Johnson Toby T   Johnson Andrew D AD   Bochud Murielle M   Rice Kenneth M KM   Henneman Peter P   Smith Albert V AV   Ehret Georg B GB   Amin Najaf N   Larson Martin G MG   Mooser Vincent V   Hadley David D   Dörr Marcus M   Bis Joshua C JC   Aspelund Thor T   Esko Tõnu T   Janssens A Cecile J W AC   Zhao Jing Hua JH   Heath Simon S   Laan Maris M   Fu Jingyuan J   Pistis Giorgio G   Luan Jian'an J   Arora Pankaj P   Lucas Gavin G   Pirastu Nicola N   Pichler Irene I   Jackson Anne U AU   Webster Rebecca J RJ   Zhang Feng F   Peden John F JF   Schmidt Helena H   Tanaka Toshiko T   Campbell Harry H   Igl Wilmar W   Milaneschi Yuri Y   Hottenga Jouke-Jan JJ   Vitart Veronique V   Chasman Daniel I DI   Trompet Stella S   Bragg-Gresham Jennifer L JL   Alizadeh Behrooz Z BZ   Chambers John C JC   Guo Xiuqing X   Lehtimäki Terho T   Kühnel Brigitte B   Lopez Lorna M LM   Polašek Ozren O   Boban Mladen M   Nelson Christopher P CP   Morrison Alanna C AC   Pihur Vasyl V   Ganesh Santhi K SK   Hofman Albert A   Kundu Suman S   Mattace-Raso Francesco U S FU   Rivadeneira Fernando F   Sijbrands Eric J G EJ   Uitterlinden Andre G AG   Hwang Shih-Jen SJ   Vasan Ramachandran S RS   Wang Thomas J TJ   Bergmann Sven S   Vollenweider Peter P   Waeber Gérard G   Laitinen Jaana J   Pouta Anneli A   Zitting Paavo P   McArdle Wendy L WL   Kroemer Heyo K HK   Völker Uwe U   Völzke Henry H   Glazer Nicole L NL   Taylor Kent D KD   Harris Tamara B TB   Alavere Helene H   Haller Toomas T   Keis Aime A   Tammesoo Mari-Liis ML   Aulchenko Yurii Y   Barroso Inês I   Khaw Kay-Tee KT   Galan Pilar P   Hercberg Serge S   Lathrop Mark M   Eyheramendy Susana S   Org Elin E   Org Elin E   Sõber Siim S   Lu Xiaowen X   Nolte Ilja M IM   Penninx Brenda W BW   Corre Tanguy T   Masciullo Corrado C   Sala Cinzia C   Groop Leif L   Voight Benjamin F BF   Melander Olle O   O'Donnell Christopher J CJ   Salomaa Veikko V   d'Adamo Adamo Pio AP   Fabretto Antonella A   Faletra Flavio F   Ulivi Sheila S   Del Greco Fabiola M F   Facheris Maurizio M   Collins Francis S FS   Bergman Richard N RN   Beilby John P JP   Hung Joseph J   Musk A William AW   Mangino Massimo M   Shin So-Youn SY   Soranzo Nicole N   Watkins Hugh H   Goel Anuj A   Hamsten Anders A   Gider Pierre P   Loitfelder Marisa M   Zeginigg Marion M   Hernandez Dena D   Najjar Samer S SS   Navarro Pau P   Wild Sarah H SH   Corsi Anna Maria AM   Singleton Andrew A   de Geus Eco J C EJ   Willemsen Gonneke G   Willemsen Gonneke G   Parker Alex N AN   Rose Lynda M LM   Buckley Brendan B   Stott David D   Orru Marco M   Uda Manuela M   van der Klauw Melanie M MM   Zhang Weihua W   Li Xinzhong X   Scott James J   Chen Yii-Der Ida YD   Burke Gregory L GL   Kähönen Mika M   Viikari Jorma J   Döring Angela A   Meitinger Thomas T   Davies Gail G   Starr John M JM   Emilsson Valur V   Plump Andrew A   Lindeman Jan H JH   Hoen Peter A C 't PA   König Inke R IR   Felix Janine F JF   Clarke Robert R   Hopewell Jemma C JC   Ongen Halit H   Breteler Monique M   Debette Stéphanie S   Destefano Anita L AL   Fornage Myriam M   Mitchell Gary F GF   Smith Nicholas L NL   Holm Hilma H   Stefansson Kari K   Thorleifsson Gudmar G   Thorsteinsdottir Unnur U   Samani Nilesh J NJ   Preuss Michael M   Rudan Igor I   Hayward Caroline C   Deary Ian J IJ   Wichmann H-Erich HE   Raitakari Olli T OT   Palmas Walter W   Kooner Jaspal S JS   Stolk Ronald P RP   Jukema J Wouter JW   Wright Alan F AF   Boomsma Dorret I DI   Bandinelli Stefania S   Gyllensten Ulf B UB   Wilson James F JF   Ferrucci Luigi L   Schmidt Reinhold R   Farrall Martin M   Spector Tim D TD   Palmer Lyle J LJ   Tuomilehto Jaakko J   Pfeufer Arne A   Gasparini Paolo P   Siscovick David D   Altshuler David D   Loos Ruth J F RJ   Toniolo Daniela D   Snieder Harold H   Gieger Christian C   Meneton Pierre P   Wareham Nicholas J NJ   Oostra Ben A BA   Metspalu Andres A   Launer Lenore L   Rettig Rainer R   Strachan David P DP   Beckmann Jacques S JS   Witteman Jacqueline C M JC   Erdmann Jeanette J   van Dijk Ko Willems KW   Boerwinkle Eric E   Boehnke Michael M   Ridker Paul M PM   Jarvelin Marjo-Riitta MR   Chakravarti Aravinda A   Abecasis Goncalo R GR   Gudnason Vilmundur V   Newton-Cheh Christopher C   Levy Daniel D   Munroe Patricia B PB   Psaty Bruce M BM   Caulfield Mark J MJ   Rao Dabeeru C DC   Tobin Martin D MD   Elliott Paul P   van Duijn Cornelia M CM  

Nature genetics 20110911 10

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31  ...[more]

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