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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

ABSTRACT: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

SUBMITTER: Kato N 

PROVIDER: S-EPMC4719169 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

Kato Norihiro N   Loh Marie M   Takeuchi Fumihiko F   Verweij Niek N   Wang Xu X   Zhang Weihua W   Kelly Tanika N TN   Saleheen Danish D   Lehne Benjamin B   Leach Irene Mateo IM   Drong Alexander W AW   Abbott James J   Wahl Simone S   Tan Sian-Tsung ST   Scott William R WR   Campanella Gianluca G   Chadeau-Hyam Marc M   Afzal Uzma U   Ahluwalia Tarunveer S TS   Bonder Marc Jan MJ   Chen Peng P   Dehghan Abbas A   Edwards Todd L TL   Esko Tõnu T   Go Min Jin MJ   Harris Sarah E SE   Hartiala Jaana J   Kasela Silva S   Kasturiratne Anuradhani A   Khor Chiea-Chuen CC   Kleber Marcus E ME   Li Huaixing H   Yu Mok Zuan Z   Nakatochi Masahiro M   Sapari Nur Sabrina NS   Saxena Richa R   Stewart Alexandre F R AFR   Stolk Lisette L   Tabara Yasuharu Y   Teh Ai Ling AL   Wu Ying Y   Wu Jer-Yuarn JY   Zhang Yi Y   Aits Imke I   Da Silva Couto Alves Alexessander A   Das Shikta S   Dorajoo Rajkumar R   Hopewell Jemma C JC   Kim Yun Kyoung YK   Koivula Robert W RW   Luan Jian'an J   Lyytikäinen Leo-Pekka LP   Nguyen Quang N QN   Pereira Mark A MA   Postmus Iris I   Raitakari Olli T OT   Scannell Bryan Molly M   Scott Robert A RA   Sorice Rossella R   Tragante Vinicius V   Traglia Michela M   White Jon J   Yamamoto Ken K   Zhang Yonghong Y   Adair Linda S LS   Ahmed Alauddin A   Akiyama Koichi K   Asif Rasheed R   Aung Tin T   Barroso Inês I   Bjonnes Andrew A   Braun Timothy R TR   Cai Hui H   Chang Li-Ching LC   Chen Chien-Hsiun CH   Cheng Ching-Yu CY   Chong Yap-Seng YS   Collins Rory R   Courtney Regina R   Davies Gail G   Delgado Graciela G   Do Loi D LD   Doevendans Pieter A PA   Gansevoort Ron T RT   Gao Yu-Tang YT   Grammer Tanja B TB   Grarup Niels N   Grewal Jagvir J   Gu Dongfeng D   Wander Gurpreet S GS   Hartikainen Anna-Liisa AL   Hazen Stanley L SL   He Jing J   Heng Chew-Kiat CK   Hixson James E JE   Hofman Albert A   Hsu Chris C   Huang Wei W   Husemoen Lise L N LLN   Hwang Joo-Yeon JY   Ichihara Sahoko S   Igase Michiya M   Isono Masato M   Justesen Johanne M JM   Katsuya Tomohiro T   Kibriya Muhammad G MG   Kim Young Jin YJ   Kishimoto Miyako M   Koh Woon-Puay WP   Kohara Katsuhiko K   Kumari Meena M   Kwek Kenneth K   Lee Nanette R NR   Lee Jeannette J   Liao Jiemin J   Lieb Wolfgang W   Liewald David C M DCM   Matsubara Tatsuaki T   Matsushita Yumi Y   Meitinger Thomas T   Mihailov Evelin E   Milani Lili L   Mills Rebecca R   Mononen Nina N   Müller-Nurasyid Martina M   Nabika Toru T   Nakashima Eitaro E   Ng Hong Kiat HK   Nikus Kjell K   Nutile Teresa T   Ohkubo Takayoshi T   Ohnaka Keizo K   Parish Sarah S   Paternoster Lavinia L   Peng Hao H   Peters Annette A   Pham Son T ST   Pinidiyapathirage Mohitha J MJ   Rahman Mahfuzar M   Rakugi Hiromi H   Rolandsson Olov O   Ann Rozario Michelle M   Ruggiero Daniela D   Sala Cinzia F CF   Sarju Ralhan R   Shimokawa Kazuro K   Snieder Harold H   Sparsø Thomas T   Spiering Wilko W   Starr John M JM   Stott David J DJ   Stram Daniel O DO   Sugiyama Takao T   Szymczak Silke S   Tang W H Wilson WHW   Tong Lin L   Trompet Stella S   Turjanmaa Väinö V   Ueshima Hirotsugu H   Uitterlinden André G AG   Umemura Satoshi S   Vaarasmaki Marja M   van Dam Rob M RM   van Gilst Wiek H WH   van Veldhuisen Dirk J DJ   Viikari Jorma S JS   Waldenberger Melanie M   Wang Yiqin Y   Wang Aili A   Wilson Rory R   Wong Tien-Yin TY   Xiang Yong-Bing YB   Yamaguchi Shuhei S   Ye Xingwang X   Young Robin D RD   Young Terri L TL   Yuan Jian-Min JM   Zhou Xueya X   Asselbergs Folkert W FW   Ciullo Marina M   Clarke Robert R   Deloukas Panos P   Franke Andre A   Franks Paul W PW   Franks Steve S   Friedlander Yechiel Y   Gross Myron D MD   Guo Zhirong Z   Hansen Torben T   Jarvelin Marjo-Riitta MR   Jørgensen Torben T   Jukema J Wouter JW   Kähönen Mika M   Kajio Hiroshi H   Kivimaki Mika M   Lee Jong-Young JY   Lehtimäki Terho T   Linneberg Allan A   Miki Tetsuro T   Pedersen Oluf O   Samani Nilesh J NJ   Sørensen Thorkild I A TIA   Takayanagi Ryoichi R   Toniolo Daniela D   Ahsan Habibul H   Allayee Hooman H   Chen Yuan-Tsong YT   Danesh John J   Deary Ian J IJ   Franco Oscar H OH   Franke Lude L   Heijman Bastiaan T BT   Holbrook Joanna D JD   Isaacs Aaron A   Kim Bong-Jo BJ   Lin Xu X   Liu Jianjun J   März Winfried W   Metspalu Andres A   Mohlke Karen L KL   Sanghera Dharambir K DK   Shu Xiao-Ou XO   van Meurs Joyce B J JBJ   Vithana Eranga E   Wickremasinghe Ananda R AR   Wijmenga Cisca C   Wolffenbuttel Bruce H W BHW   Yokota Mitsuhiro M   Zheng Wei W   Zhu Dingliang D   Vineis Paolo P   Kyrtopoulos Soterios A SA   Kleinjans Jos C S JCS   McCarthy Mark I MI   Soong Richie R   Gieger Christian C   Scott James J   Teo Yik-Ying YY   He Jiang J   Elliott Paul P   Tai E Shyong ES   van der Harst Pim P   Kooner Jaspal S JS   Chambers John C JC  

Nature genetics 20150921 11

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the reg  ...[more]

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