در این مقاله بخشی از ترجمه مقاله ایی قرار گرفته است که از انگلیسی به فارسی بوده و تاثیرات فشار خون بر بیماری های مختلف و اثر ژنتیک بر فشار خون را مورد بررسی قرار می دهد این مقاله گسترده بوده و شامل جداول زیادی می باشد که داده هایی را در این مورد در مقاله قرار داده است . اصل مفاله به صورت انگلیسی بوده و دارای 20 صفحه به صورت pdf می باشد و متن ترجمه شده تقریبا 11 صفحه به صورت word است.

خلاصه متن

فشار خون یک مشکل عمده در حوزه سلامت در جهان می باشد که در ارتباط با قلب و عروق و بیماری های عروق مغزی می باشد. به خوبی این موضوع اثبات شده است که  فشار خون به طور معمول به صورت فنوتیپ پیچیده بوده و تحت تاثیر ژن های چندگانه و عوامل محیطی می باشد . ابزار های معمول ژن شناسی این امکان را فراهم آورده است که برای انواع ژن های میلیونی در میان ژن های انسان امکان شناسایی را فراهم آورده است , و به طرز قابل اطمینانی این شرایط را مقرون به صرفه کرده است , که موضوع تحقیقات ژن شناسی را به مکان های دیگر را فراهم آورده است . همکاری های بین المللی / کنسرسیوم های بین المللی این امکان را برای استفاده از  ژن شناسی  نمونه های کوچک برای کشف ژن ها و همانند سازی فراهم آورده است . ژنوم های گسترده در ارتباط با  مطالعات این چنین گزارش داده اند که بیشتر از 60 مورد ارتباط بین فشار خون و ژن وجود دارد , از اکثر این نظر ها انتظار نمی رود هیچ ارتباطی بین فرضیه ها وجود داشته باشد . در نقطه مقابل برای پیوند هایی می تواند برقرار شود و بعضی ژن ها به صورت انتخابی مورد مطالعه قرار می گیرند. این یافته ها پتانسیل هایی را در خود مورد هدف قرار داده اند تا دارو درمانی و یافتن راه حل ها  برای پیشگیری و درمان فشار خون مورد استفاده قرار بگیرند. اگرچه فقط بخش کوچکی از تغییر فشار خون در حد بالایی ارتباطی با  ژنتیک ندارد . بیشتر مدل ها شبیه به نمونه های کوچک تر هستند , مطالعه ژن ها  و واکنش های محیطی به وسیله ی کاوش با فرکانس  پایین یا فرکانس هایی که کمیاب هستند به دست می آید . پیشرفت در اپی ژنتیک با بررسی تنوع هایی زیادی در صفات ایجاد می کند باعث نمی شود تفاوتی در توالی dna ایجاد نمی کند , این در حالی است که آشکار سازی یک کلاس از ژن های جدید و مهم برای فشار خون وجود دارد .

متن انگلیسی:

Abstract

Hypertension is a major global health problem associated with cardiovascular and

cerebrovascular diseases. It is well established that blood pressure and hypertension

are common complex phenotypes affected by multiple genetic and environmental

1. Contemporary genomic tools make it possible to genotype millions of genetic

variants across the human genome in an efficient, reliable, and cost-effective manner,

which has transformed hypertension genetics research. International collaborations/

consortia have enabled the use of unprecedentedly large sample sizes for gene discovery

and replication. Genome-wide association studies have reported more than 60 loci

associated with blood pressure or hypertension, most of which were not expected to

have any association with these phenotypes. In contrast to linkage and candidate gene

studies, the reproducibility of genome-wide association studies is much higher and

some results have been verified across different ethnicities. These novel findings have

provided potential targets for pharmacotherapy and clues for personalized prevention

and treatment of hypertension. Although only a small proportion of blood pressure

variation is attributed to the genetic variants identified so far, more variants are likely to

be discovered by employing larger sample sizes, studying gene–environment interactions,

or by exploring low-frequency or rare variants. Advances in epigenetics, which

examines trait variation not caused by differences in DNA sequences, will probably

reveal a new and important class of genetic components for hypertension.

Keywords: Blood pressure, Hypertension, Genetics, Genome-wide association study,

Genes

منابع:

Adeyemo A, Gerry N, Chen G, Herbert A, Doumatey A, Huang H, Zhou J, Lashley K, Chen Y, Christman M, Rotimi C

(2009) A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genet

5(7):e1000564. doi:10.1371/journal.pgen.1000564

Baccarelli A, Rienstra M, Benjamin EJ (2010) Cardiovascular epigenetics: basic concepts and results from animal and

human studies. Circ Cardiovasc Genet 3(6):567–573. doi:10.1161/CIRCGENETICS.110.958744

Basson J, Simino J, Rao DC (2012) Between candidate genes and whole genomes: time for alternative approaches in

blood pressure genetics. Curr Hypertens Rep 14(1):46–61. doi:10.1007/s11906-011-0241-8

Basson JJ, de las Fuentes L, Rao DC (2014a) Single nucleotide polymorphism-single nucleotide polymorphism interactions

among inflammation genes in the genetic architecture of blood pressure in the Framingham Heart Study. Am

J Hypertens 28(2):248–255. doi:10.1093/ajh/hpu132

Basson J, Sung YJ, Schwander K, Kume R, Simino J, de las Fuentes L, Rao DC (2014b) Gene–education interactions identify

novel blood pressure loci in the Framingham Heart Study. Am J Hypertens 27(3):431–444. doi:10.1093/ajh/hpt283

Binder A (2007) A review of the genetics of essential hypertension. Curr Opin Cardiol 22(3):176–184. doi:10.1097/

1. 0b013e3280d357f9

Zheng et al. Appl Inform (2015) 2:10 Page 15 of 20

Carretero OA, Oparil S (2000) Essential hypertension. Part I: definition and etiology. Circulation 101(3):329–335.

doi:10.1161/01.CIR.101.3.329

Charchar F, Zimmerli L, Tomaszewski M (2008) The pressure of finding human hypertension genes: new tools, old dilemmas.

J Hum Hypertens 22(12):821–828. doi:10.1038/jhh.2008.67

Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M, Cha SH, Kim JW, Han BG, Min H, Ahn Y, Park

MS, Han HR, Jang HY, Cho EY, Lee JE, Cho NH, Shin C, Park T, Park JW, Lee JK, Cardon L, Clarke G, McCarthy MI, Lee JY,

Lee JK, Oh B, Kim HL (2009) A large-scale genome-wide association study of Asian populations uncovers genetic

factors influencing eight quantitative traits. Nat Genet 41(5), pp. 527–34, doi: 10.1038/ng.357

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella

EJ, the National High Blood Pressure Education Program Coordinating Committee (2003) The seventh report of the

joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7

1. JAMA 289(19):2560–2571. doi:10.1001/jama.289.19.2560

Collins FS, Varmus H (2015) A new initiative on precision medicine. N Engl J Med 372(9):793–795. doi:10.1056/

NEJMp1500523

Cowley AW Jr, Nadeau JH, Baccarelli A, Berecek K, Fornage M, Gibbons GH, Harrison DG, Liang M, Nathanielsz PW,

O’Connor DT, Ordovas J, Peng W, Soares MB, Szyf M, Tolunay HE, Wood KC, Zhao K, Galis ZS (2012) Report of the

National Heart, Lung, and Blood Institute Working Group on epigenetics and hypertension. Hypertension 59(5):899–

1. doi:10.1161/HYPERTENSIONAHA.111.190116

Ehret GB, Caulfield MJ (2013) Genes for blood pressure: an opportunity to understand hypertension. Eur Heart J

34(13):951–961. doi:10.1093/eurheartj/ehs455

Fan JB, Chen X, Halushka MK, Berno A, Huang X, Ryder T, Lipshutz RJ, Lockhart DJ, Chakravarti A (2000) Parallel genotyping

of human SNPs using generic high-density oligonucleotide tag arrays. Genome Res 10(6):853–860. doi:10.1101/

1. 10.6.853

Fox ER, Young JH, Li Y, Dreisbach AW, Keating BJ, Musani SK, Liu K, Morrison AC, Ganesh S, Kutlar A, Ramachandran

VS, Polak JF, Fabsitz RR, Dries DL, Farlow DN, Redline S, Adeyemo A, Hirschorn JN, Sun YV, Wyatt SB, Penman AD,

Palmas W, Rotter JI, Townsend RR, Doumatey AP, Tayo BO, Mosley TH Jr, Lyon HN, Kang SJ, Rotimi CN, Cooper RS,

Franceschini N, Curb JD, Martin LW, Eaton CB, Kardia SL, Taylor HA, Caulfield MJ, Ehret GB, Johnson T; International

Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), Chakravarti A, Zhu X, Levy D (2011)

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate

Gene Association Resource study. Hum Mol Genet 20(11):2273–2284. doi:10.1093/hmg/ddr092

Franceschini N, Fox E, Zhang Z, Edwards TL, Nalls MA, Sung YJ, Tayo BO, Sun YV, Gottesman O, Adeyemo A, Johnson AD,

Young JH, Rice K, Duan Q, Chen F, Li Y, Tang H, Fornage M, Keene KL, Andrews JS, Smith JA, Faul JD, Guangfa Z, Guo

W, Liu Y, Murray SS, Musani SK, Srinivasan S, Velez Edwards DR, Wang H, Becker LC, Bovet P, Bochud M, Broeckel U,

Burnier M, Carty C, Chasman DI, Ehret G, Chen WM, Chen G, Chen W, Ding J, Dreisbach AW, Evans MK, Guo X, Garcia

ME, Jensen R, Keller MF, Lettre G, Lotay V, Martin LW, Moore JH, Morrison AC, Mosley TH, Ogunniyi A, Palmas W,

Papanicolaou G, Penman A, Polak JF, Ridker PM, Salako B, Singleton AB, Shriner D, Taylor KD, Vasan R, Wiggins K, Williams

SM, Yanek LR, Zhao W, Zonderman AB, Becker DM, Berenson G, Boerwinkle E, Bottinger E, Cushman M, Eaton

C, Nyberg F, Heiss G, Hirschhron JN, Howard VJ, Karczewsk KJ, Lanktree MB, Liu K, Liu Y, Loos R, Margolis K, Snyder M;

Asian Genetic Epidemiology Network Consortium, Psaty BM, Schork NJ, Weir DR, Rotimi CN, Sale MM, Harris T, Kardia

SL, Hunt SC, Arnett D, Redline S, Cooper RS, Risch NJ, Rao DC, Rotter JI, Chakravarti A, Reiner AP, Levy D, Keating

BJ, Zhu X (2013) Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals

common associated genes in African and non-African populations. Am J Hum Genet 93(3):545–554. doi:10.1016/j.

1. 2013.07.010

Ganesh SK, Tragante V, Guo W, Guo Y, Lanktree MB, Smith EN, Johnson T, Castillo BA, Barnard J, Baumert J, Chang YP,

Elbers CC, Farrall M, Fischer ME, Franceschini N, Gaunt TR, Gho JM, Gieger C, Gong Y, Isaacs A, Kleber ME, Mateo

Leach I, McDonough CW, Meijs MF, Mellander O, Molony CM, Nolte IM, Padmanabhan S, Price TS, Rajagopalan R,

Shaffer J, Shah S, Shen H, Soranzo N, van der Most PJ, Van Iperen EP, Van Setten J, Vonk JM, Zhang L, Beitelshees AL,

Berenson GS, Bhatt DL, Boer JM, Boerwinkle E, Burkley B, Burt A, Chakravarti A, Chen W, Cooper-Dehoff RM, Curtis SP,

Dreisbach A, Duggan D, Ehret GB, Fabsitz RR, Fornage M, Fox E, Furlong CE, Gansevoort RT, Hofker MH, Hovingh GK,

Kirkland SA, Kottke-Marchant K, Kutlar A, Lacroix AZ, Langaee TY, Li YR, Lin H, Liu K, Maiwald S, Malik R; CARDIOGRAM,

METASTROKE, Murugesan G, Newton-Cheh C, O’Connell JR, Onland-Moret NC, Ouwehand WH, Palmas W,

Penninx BW, Pepine CJ, Pettinger M, Polak JF, Ramachandran VS, Ranchalis J, Redline S, Ridker PM, Rose LM, Scharnag

H, Schork NJ, Shimbo D, Shuldiner AR, Srinivasan SR, Stolk RP, Taylor HA, Thorand B, Trip MD, van Duijn CM, Verschuren

WM, Wijmenga C, Winkelmann BR, Wyatt S, Young JH, Boehm BO, Caulfield MJ, Chasman DI, Davidson KW,

Doevendans PA, Fitzgerald GA, Gums JG, Hakonarson H, Hillege HL, Illig T, Jarvik GP, Johnson JA, Kastelein JJ, Koenig

W; LifeLines Cohort Study, Mنrz W, Mitchell BD, Murray SS, Oldehinkel AJ, Rader DJ, Reilly MP, Reiner AP, Schadt EE,

Silverstein RL, Snieder H, Stanton AV, Uitterlinden AG, van der Harst P, van der Schouw YT, Samani NJ, Johnson AD,

Munroe PB, de Bakker PI, Zhu X, Levy D, Keating BJ, Asselbergs FW (2013) Loci influencing blood pressure identified

using a cardiovascular gene-centric array. Hum Mol Genet 22(8):1663–1678. doi:10.1093/hmg/dds555

Ganesh SK, Chasman DI, Larson MG, Guo X, Verwoert G, Bis JC, Gu X, Smith AV, Yang ML, Zhang Y, Ehret G, Rose LM,

Hwang SJ, Papanicolau GJ, Sijbrands EJ, Rice K, Eiriksdottir G, Pihur V, Ridker PM, Vasan RS, Newton-Cheh C; Global

Blood Pressure Genetics Consortium, Raffel LJ, Amin N, Rotter JI, Liu K, Launer LJ, Xu M, Caulfield M, Morrison AC,

Johnson AD, Vaidya D, Dehghan A, Li G, Bouchard C, Harris TB, Zhang H, Boerwinkle E, Siscovick DS, Gao W, Uitterlinden

AG, Rivadeneira F, Hofman A, Willer CJ, Franco OH, Huo Y, Witteman JC, Munroe PB, Gudnason V, Palmas

W, van Duijn C, Fornage M, Levy D, Psaty BM, Chakravarti A (2014) Effects of long-term averaging of quantitative

blood pressure traits on the detection of genetic associations. Am J Hum Genet 95(1):49–65. doi:10.1016/j.

1. 2014.06.002

Genomes Project Consortium (2012) An integrated map of genetic variation from 1092 human genomes. Nature

491(7422):56–65. doi:10.1038/nature11632

Hamet P, Pausova Z, Adarichev V, Adaricheva K, Tremblay J (1998) Hypertension: genes and environment. J Hypertens

16(4):397–418

Zheng et al. Appl Inform (2015) 2:10 Page 16 of 20

He J, Kelly TN, Zhao Q, Li H, Huang J, Wang L, Jaquish CE, Sung YJ, Shimmin LC, Lu F, Mu J, Hu D, Ji X, Shen C, Guo D, Ma

J, Wang R, Shen J, Li S, Chen J, Mei H, Chen CS, Chen S, Chen J, Li J, Cao J, Lu X, Wu X, Rice TK, Gu CC, Schwander K,

Hamm LL, Liu D, Rao DC, Hixson JE, Gu D (2013) Genome-wide association study identifies 8 novel loci associated

with blood pressure responses to interventions in Han Chinese. Circ Cardiovasc Genet 6(6):598–607. doi:10.1161/

1. 113.000307

Ho JE, Levy D, Rose L, Johnson AD, Ridker PM, Chasman DI (2011) Discovery and replication of novel blood pressure

genetic loci in the Women’s Genome Health Study. J Hypertens 29(1):62–69. doi:10.1097/HJH.0b013e3283406927

Hong KW, Jin HS, Lim JE, Kim S, Go MJ, Oh B (2010) Recapitulation of two genomewide association studies on blood

pressure and essential hypertension in the Korean population. J Hum Genet 55(6):336–341. doi:10.1038/jhg.2010.31

Hong KW, Min H, Heo BM, Joo SE, Kim SS, Kim Y (2012) Recapitulation of genome-wide association studies on pulse pressure

and mean arterial pressure in the Korean population. J Hum Genet 57(6):391–393. doi:10.1038/jhg.2012.31

International Consortium for Blood Pressure Genome-Wide Association Studies (2011) Genetic variants in novel pathways

influence blood pressure and cardiovascular disease risk. Nature 478(7367):103–109. doi:10.1038/nature10405

International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320.

doi:10.1038/nature04226

International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature

449(7164):851–861. doi:10.1038/nature06258

Ji W, Foo JN, O’Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP (2008) Rare independent

mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40(5):592–599.

doi:10.1038/ng.118

Johnson AD, Newton-Cheh C, Chasman DI, Ehret GB, Johnson T, Rose L, Rice K, Verwoert GC, Launer LJ, Gudnason V,

Larson MG, Chakravarti A, Psaty BM, Caulfield M, van Duijn CM, Ridker PM, Munroe PB, Levy D, Cohorts for Heart and

Aging Research in Genomic Epidemiology Consortium, Global BPgen Consortium, Women’s Genome Health Study

(2011a) Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals.

Hypertension 57(5):903–910. doi:10.1161/HYPERTENSIONAHA.110.158667

Johnson T, Gaunt TR, Newhouse SJ, Padmanabhan S, Tomaszewski M, Kumari M, Morris RW, Tzoulaki I, O’Brien ET, Poulter

NR, Sever P, Shields DC, Thom S, Wannamethee SG, Whincup PH, Brown MJ, Connell JM, Dobson RJ, Howard PJ, Mein

CA, Onipinla A, Shaw-Hawkins S, Zhang Y, Davey Smith G, Day IN, Lawlor DA, Goodall AH; Cardiogenics Consortium,

Fowkes FG, Abecasis GR, Elliott P, Gateva V; Global BPgen Consortium, Braund PS, Burton PR, Nelson CP, Tobin MD,

van der Harst P, Glorioso N, Neuvrith H, Salvi E, Staessen JA, Stucchi A, Devos N, Jeunemaitre X, Plouin PF, Tichet J,

Juhanson P, Org E, Putku M, Sُber S, Veldre G, Viigimaa M, Levinsson A, Rosengren A, Thelle DS, Hastie CE, Hedner

T, Lee WK, Melander O, Wahlstrand B, Hardy R, Wong A, Cooper JA, Palmen J, Chen L, Stewart AF, Wells GA, Westra

HJ, Wolfs MG, Clarke R, Franzosi MG, Goel A, Hamsten A, Lathrop M, Peden JF, Seedorf U, Watkins H, Ouwehand WH,

Sambrook J, Stephens J, Casas JP, Drenos F, Holmes MV, Kivimaki M, Shah S, Shah T, Talmud PJ, Whittaker J, Wallace C,

Delles C, Laan M, Kuh D, Humphries SE, Nyberg F, Cusi D, Roberts R, Newton-Cheh C, Franke L, Stanton AV, Dominiczak

AF, Farrall M, Hingorani AD, Samani NJ, Caulfield MJ, Munroe PB (2011) Blood pressure loci identified with a

gene-centric array. Am J Hum Genet 89(6):688–700. doi:10.1016/j.ajhg.2011.10.013

Kamide K, Asayama K, Katsuya T, Ohkubo T, Hirose T, Inoue R, Metoki H, Kikuya M, Obara T, Hanada H, Thijs L, Kuznetsova

T, Noguchi Y, Sugimoto K, Ohishi M, Morimoto S, Nakahashi T, Takiuchi S, Ishimitsu T, Tsuchihashi T, Soma M, Higaki

J, Matsuura H, Shinagawa T, Sasaguri T, Miki T, Takeda K, Shimamoto K, Ueno M, Hosomi N, Kato J, Komai N, Kojima

S, Sase K, Miyata T, Tomoike H, Kawano Y, Ogihara T, Rakugi H, Staessen JA, Imai Y, GEANE study group, HOMEDBP

study group (2013) Genome-wide response to antihypertensive medication using home blood pressure

measurements: a pilot study nested within the HOMED-BP study. Pharmacogenomics 14:1709–1721. doi:10.2217/

1. 13.161

Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, Tay WT, Chen CH, Zhang Y, Yamamoto K, Katsuya T, Yokota M, Kim YJ,

Ong RT, Nabika T, Gu D, Chang LC, Kokubo Y, Huang W, Ohnaka K, Yamori Y, Nakashima E, Jaquish CE, Lee JY, Seielstad

M, Isono M, Hixson JE, Chen YT, Miki T, Zhou X, Sugiyama T, Jeon JP, Liu JJ, Takayanagi R, Kim SS, Aung T, Sung

YJ, Zhang X, Wong TY, Han BG, Kobayashi S, Ogihara T, Zhu D, Iwai N, Wu JY, Teo YY, Tai ES, Cho YS, He J (2011) Metaanalysis

of genome-wide association studies identifies common variants associated with blood pressure variation in

east Asians. Nat Genet 43(6):531–538. doi:10.1038/ng.834

Keating BJ, Tischfield S, Murray SS, Bhangale T, Price TS, Glessner JT, Galver L, Barrett JC, Grant SF, Farlow DN, Chandrupatla

HR, Hansen M, Ajmal S, Papanicolaou GJ, Guo Y, Li M, Derohannessian S, de Bakker PI, Bailey SD, Montpetit A,

Edmondson AC, Taylor K, Gai X, Wang SS, Fornage M, Shaikh T, Groop L, Boehnke M, Hall AS, Hattersley AT, Frackelton

E, Patterson N, Chiang CW, Kim CE, Fabsitz RR, Ouwehand W, Price AL, Munroe P, Caulfield M, Drake T, Boerwinkle

E, Reich D, Whitehead AS, Cappola TP, Samani NJ, Lusis AJ, Schadt E, Wilson JG, Koenig W, McCarthy MI, Kathiresan

S, Gabriel SB, Hakonarson H, Anand SS, Reilly M, Engert JC, Nickerson DA, Rader DJ, Hirschhorn JN, Fitzgerald GA

(2008) Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic

association studies. PLoS One 3(10):e3583. doi:10.1371/journal.pone.0003583

Kelly TN, Takeuchi F, Tabara Y, Edwards TL, Kim YJ, Chen P, Li H, Wu Y, Yang CF, Zhang Y, Gu D, Katsuya T, Ohkubo T, Gao YT,

Go MJ, Teo YY, Lu L, Lee NR, Chang LC, Peng H, Zhao Q, Nakashima E, Kita Y, Shu XO, Kim NH, Tai ES, Wang Y, Adair LS,

Chen CH, Zhang S, Li C, Nabika T, Umemura S, Cai Q, Cho YS, Wong TY, Zhu J, Wu JY, Gao X, Hixson JE, Cai H, Lee J,

Cheng CY, Rao DC, Xiang YB, Cho MC, Han BG, Wang A, Tsai FJ, Mohlke K, Lin X, Ikram MK, Lee JY, Zheng W, Tetsuro

M, Kato N, He J (2013) Genome-wide association study meta-analysis reveals transethnic replication of mean arterial

and pulse pressure loci. Hypertension 62(5):853–859. doi:10.1161/HYPERTENSIONAHA.113.01148

Kraft P, Yen YC, Stram DO, Morrison J, Gauderman WJ (2007) Exploiting gene–environment interaction to detect genetic

1. Hum Hered 63(2):111–119. doi:10.1159/000099183

Kunes J, Zicha J (2009) The interaction of genetic and environmental factors in the etiology of hypertension. Physiol Res

58(Suppl 2):S33–S41

Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ, Vasan RS, Mitchell GF (2007) Framingham Heart

Study 100 K Project: genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet 8(Suppl

1):S3. doi:10.1186/1471-2350-8-S1-S3

Zheng et al. Appl Inform (2015) 2:10 Page 17 of 20

Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko

Y, Lumley T, Kِttgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace-Raso FU, Smith

AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O’Donnell CJ, Hofman A, Rotter JI, Coresh

J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JC, Boerwinkle E, Wang TJ, Gudnason V, Larson MG,

Chakravarti A, Psaty BM, van Duijn CM (2009) Genome-wide association study of blood pressure and hypertension.

Nat Genet 41(6):677–687. doi:10.1038/ng.384

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Collaboration Prospective Studies (2002) Age-specific relevance of

usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective

1. Lancet 360(9349):1903–1913. doi:10.1016/S0140-6736(02)11911-8

Li Y, Abecasis GR (2006) Mach 1.0: Rapid haplotype reconstruction and missing genotype inference. Am J Hum Genet

S79:2290

Lifton RP (1996) Molecular genetics of human blood pressure variation. Science 272(5262):676–680. doi:10.1126/

1. 272.5262.676

Lin Y, Lai X, Chen B, Xu Y, Huang B, Chen Z, Zhu S, Yao J, Jiang Q, Huang H, Wen J, Chen G (2011) Genetic variations in

CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in She ethnic minority of

1. Atherosclerosis 219(2):709–714. doi:10.1016/j.atherosclerosis.2011.09.006

Lu X, Wang L, Lin X, Huang J, Charles GuC, He M, Shen H, He J, Zhu J, Li H, Hixson JE, Wu T, Dai J, Lu L, Shen C, Chen S, He

L, Mo Z, Hao Y, Mo X, Yang X, Li J, Cao J, Chen J, Fan Z, Li Y, Zhao L, Li H, Lu F, Yao C, Yu L, Xu L, Mu J, Wu X, Deng Y, Hu

D, Zhang W, Ji X, Guo D, Guo Z, Zhou Z, Yang Z, Wang R, Yang J, Zhou X, Yan W, Sun N, Gao P, Gu D (2014) Genomewide

association study in Chinese identifies novel loci for blood pressure and hypertension. Hum Mol Genet

24(3):865–874. doi:10.1093/hmg/ddu478

Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A,

Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark

AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of

complex diseases. Nature 461(7265):747–753. doi:10.1038/nature08494

Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genomewide association studies

by imputation of genotypes. Nat Genet 39(7):906–913. doi:10.1038/ng2088

Metzker ML (2010) Sequencing technologies—the next generation. Nat Rev Genet 11(1):31–46. doi:10.1038/nrg2626

Miall WE, Oldham PD (1963) The hereditary factor in arterial blood-pressure. Br Med J 1(5323):75–80. doi:10.1136/

1. 1.5323.75

Morrison AC, Bis JC, Hwang SJ, Ehret GB, Lumley T, Rice K, Muzny D, Gibbs RA, Boerwinkle E, Psaty BM, Chakravarti A,

Levy D (2014) Sequence analysis of six blood pressure candidate regions in 4178 individuals: the Cohorts for Heart

and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study. PLoS One 9(10):e109155.

doi:10.1371/journal.pone.0109155

Neal B, MacMahon S, Chapman N, Blood Pressure Lowering Treatment Trialists’ Collaboration (2000) Effects of ACE inhibitors,

calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of

randomised trials. Lancet 356(9246):1955–1964. doi:10.1016/S0140-6736(00)03307-9

Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S,

Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der

Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto

J, Burton PR, Hadley D, McArdle WL; Wellcome Trust Case Control Consortium, Brown M, Dominiczak A, Newhouse

SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth

DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V,

Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle

LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Dِring A, Gieger

C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O’Donnell CJ, Schwartz SM, Siscovick

DS, Subirana I, Freimer NB, Hartikainen AL, McCarthy MI, O’Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van

Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF, Seedorf U, Syvنnen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P,

Schlessinger D, Scuteri A, Dِrr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Vِlker U, Galan P, Gut

IG, Hercberg S, Lathrop GM, Zelenika D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R,

Forouhi NG, Vِlzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA,

Kooner JS, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan

M, Meneton P, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RJ, Elliott P, Abecasis GR, Caulfield M,

Munroe PB (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet

41(6):666–676. doi:10.1038/ng.361

Nguyen KD, Pihur V, Ganesh SK, Rakha A, Cooper RS, Hunt SC, Freedman BI, Coresh J, Kao WH, Morrison AC, Boerwinkle E,

Ehret GB, Chakravarti A (2013) Effects of rare and common blood pressure gene variants on essential hypertension:

results from the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities studies. Circ Res

112(2):318–326. doi:10.1161/CIRCRESAHA.112.276725

Org E, Eyheramendy S, Juhanson P, Gieger C, Lichtner P, Klopp N, Veldre G, Dِring A, Viigimaa M, Sُber S, Tomberg K,

Eckstein G; KORA, Kelgo P, Rebane T, Shaw-Hawkins S, Howard P, Onipinla A, Dobson RJ, Newhouse SJ, Brown M,

Dominiczak A, Connell J, Samani N, Farrall M; BRIGHT, Caulfield MJ, Munroe PB, Illig T, Wichmann HE, Meitinger T,

Laan M (2009) Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure

determination in two European populations. Hum Mol Genet 18(12):2288–2296. doi:10.1093/hmg/ddp135

Padmanabhan S, Melander O, Johnson T, Di Blasio AM, Lee WK, Gentilini D, Hastie CE, Menni C, Monti MC, Delles C,

Laing S, Corso B, Navis G, Kwakernaak AJ, van der Harst P, Bochud M, Maillard M, Burnier M, Hedner T, Kjeldsen S,

Wahlstrand B, Sjِgren M, Fava C, Montagnana M, Danese E, Torffvit O, Hedblad B, Snieder H, Connell JM, Brown M,

Samani NJ, Farrall M, Cesana G, Mancia G, Signorini S, Grassi G, Eyheramendy S, Wichmann HE, Laan M, Strachan

DP, Sever P, Shields DC, Stanton A, Vollenweider P, Teumer A, Vِlzke H, Rettig R, Newton-Cheh C, Arora P, Zhang

F, Soranzo N, Spector TD, Lucas G, Kathiresan S, Siscovick DS, Luan J, Loos RJ, Wareham NJ, Penninx BW, Nolte

IM, McBride M, Miller WH, Nicklin SA, Baker AH, Graham D, McDonald RA, Pell JP, Sattar N, Welsh P; Global BPgen

Zheng et al. Appl Inform (2015) 2:10 Page 18 of 20

Consortium, Munroe P, Caulfield MJ, Zanchetti A, Dominiczak AF (2010) Genome-wide association study of blood

pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet 6(10):e1001177.

doi:10.1371/journal.pgen.1001177

Padmanabhan S, Caulfield M, Dominiczak AF (2015) Genetic and molecular aspects of hypertension. Circ Res 116(6):937–

1. doi:10.1161/CIRCRESAHA.116.303647

Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R, Forrester T, Allison DB, Deka R, Ferrell RE, Shriver MD

(1998) Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet

63(6):1839–1851. doi:10.1086/302148

Pe’er I, Yelensky R, Altshuler D, Daly MJ (2008) Estimation of the multiple testing burden for genomewide association

studies of nearly all common variants. Genet Epidemiol 32(4):381–385. doi:10.1002/gepi.20303

Pickering G (1965) Hyperpiesis: high blood-pressure without evident cause: essential hypertension. Br Med J

2(5468):959–968

Qi Y, Zhao H, Wang Y, Wang Y, Lu C, Xiao Y, Cao J, Jia N, Wang B, Niu W (2014) Replication of the top 10 most significant

polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East

1. Hypertens Res 37(2):134–138. doi:10.1038/hr.2013.132

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-

Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J,

Thom T, Wasserthiel-Smoller S, Hong Y, American Heart Association Statistics Committee and Stroke Statistics

S