@article {1325, title = {Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.}, journal = {Nature}, volume = {478}, year = {2011}, month = {2011 Sep 11}, pages = {103-9}, abstract = {

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>=140 mm Hg systolic blood pressure or >=90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

}, keywords = {Africa, Asia, Blood Pressure, Cardiovascular Diseases, Coronary Artery Disease, Europe, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Kidney Diseases, Polymorphism, Single Nucleotide, Stroke}, issn = {1476-4687}, doi = {10.1038/nature10405}, author = {Ehret, Georg B and Munroe, Patricia B and Rice, Kenneth M and Bochud, Murielle and Johnson, Andrew D and Chasman, Daniel I and Smith, Albert V and Tobin, Martin D and Verwoert, Germaine C and Hwang, Shih-Jen and Pihur, Vasyl and Vollenweider, Peter and O{\textquoteright}Reilly, Paul F and Amin, Najaf and Bragg-Gresham, Jennifer L and Teumer, Alexander and Glazer, Nicole L and Launer, Lenore and Zhao, Jing Hua and Aulchenko, Yurii and Heath, Simon and S{\~o}ber, Siim and Parsa, Afshin and Luan, Jian{\textquoteright}an and Arora, Pankaj and Dehghan, Abbas and Zhang, Feng and Lucas, Gavin and Hicks, Andrew A and Jackson, Anne U and Peden, John F and Tanaka, Toshiko and Wild, Sarah H and Rudan, Igor and Igl, Wilmar and Milaneschi, Yuri and Parker, Alex N and Fava, Cristiano and Chambers, John C and Fox, Ervin R and Kumari, Meena and Go, Min Jin and van der Harst, Pim and Kao, Wen Hong Linda and Sj{\"o}gren, Marketa and Vinay, D G and Alexander, Myriam and Tabara, Yasuharu and Shaw-Hawkins, Sue and Whincup, Peter H and Liu, Yongmei and Shi, Gang and Kuusisto, Johanna and Tayo, Bamidele and Seielstad, Mark and Sim, Xueling and Nguyen, Khanh-Dung Hoang and Lehtim{\"a}ki, Terho and Matullo, Giuseppe and Wu, Ying and Gaunt, Tom R and Onland-Moret, N Charlotte and Cooper, Matthew N and Platou, Carl G P and Org, Elin and Hardy, Rebecca and Dahgam, Santosh and Palmen, Jutta and Vitart, Veronique and Braund, Peter S and Kuznetsova, Tatiana and Uiterwaal, Cuno S P M and Adeyemo, Adebowale and Palmas, Walter and Campbell, Harry and Ludwig, Barbara and Tomaszewski, Maciej and Tzoulaki, Ioanna and Palmer, Nicholette D and Aspelund, Thor and Garcia, Melissa and Chang, Yen-Pei C and O{\textquoteright}Connell, Jeffrey R and Steinle, Nanette I and Grobbee, Diederick E and Arking, Dan E and Kardia, Sharon L and Morrison, Alanna C and Hernandez, Dena and Najjar, Samer and McArdle, Wendy L and Hadley, David and Brown, Morris J and Connell, John M and Hingorani, Aroon D and Day, Ian N M and Lawlor, Debbie A and Beilby, John P and Lawrence, Robert W and Clarke, Robert and Hopewell, Jemma C and Ongen, Halit and Dreisbach, Albert W and Li, Yali and Young, J Hunter and Bis, Joshua C and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Adair, Linda S and Lee, Nanette R and Chen, Ming-Huei and Olden, Matthias and Pattaro, Cristian and Bolton, Judith A Hoffman and K{\"o}ttgen, Anna and Bergmann, Sven and Mooser, Vincent and Chaturvedi, Nish and Frayling, Timothy M and Islam, Muhammad and Jafar, Tazeen H and Erdmann, Jeanette and Kulkarni, Smita R and Bornstein, Stefan R and Gr{\"a}ssler, J{\"u}rgen and Groop, Leif and Voight, Benjamin F and Kettunen, Johannes and Howard, Philip and Taylor, Andrew and Guarrera, Simonetta and Ricceri, Fulvio and Emilsson, Valur and Plump, Andrew and Barroso, In{\^e}s and Khaw, Kay-Tee and Weder, Alan B and Hunt, Steven C and Sun, Yan V and Bergman, Richard N and Collins, Francis S and Bonnycastle, Lori L and Scott, Laura J and Stringham, Heather M and Peltonen, Leena and Perola, Markus and Vartiainen, Erkki and Brand, Stefan-Martin and Staessen, Jan A and Wang, Thomas J and Burton, Paul R and Soler Artigas, Maria and Dong, Yanbin and Snieder, Harold and Wang, Xiaoling and Zhu, Haidong and Lohman, Kurt K and Rudock, Megan E and Heckbert, Susan R and Smith, Nicholas L and Wiggins, Kerri L and Doumatey, Ayo and Shriner, Daniel and Veldre, Gudrun and Viigimaa, Margus and Kinra, Sanjay and Prabhakaran, Dorairaj and Tripathy, Vikal and Langefeld, Carl D and Rosengren, Annika and Thelle, Dag S and Corsi, Anna Maria and Singleton, Andrew and Forrester, Terrence and Hilton, Gina and McKenzie, Colin A and Salako, Tunde and Iwai, Naoharu and Kita, Yoshikuni and Ogihara, Toshio and Ohkubo, Takayoshi and Okamura, Tomonori and Ueshima, Hirotsugu and Umemura, Satoshi and Eyheramendy, Susana and Meitinger, Thomas and Wichmann, H-Erich and Cho, Yoon Shin and Kim, Hyung-Lae and Lee, Jong-Young and Scott, James and Sehmi, Joban S and Zhang, Weihua and Hedblad, Bo and Nilsson, Peter and Smith, George Davey and Wong, Andrew and Narisu, Narisu and Stan{\v c}{\'a}kov{\'a}, Alena and Raffel, Leslie J and Yao, Jie and Kathiresan, Sekar and O{\textquoteright}Donnell, Christopher J and Schwartz, Stephen M and Ikram, M Arfan and Longstreth, W T and Mosley, Thomas H and Seshadri, Sudha and Shrine, Nick R G and Wain, Louise V and Morken, Mario A and Swift, Amy J and Laitinen, Jaana and Prokopenko, Inga and Zitting, Paavo and Cooper, Jackie A and Humphries, Steve E and Danesh, John and Rasheed, Asif and Goel, Anuj and Hamsten, Anders and Watkins, Hugh and Bakker, Stephan J L and van Gilst, Wiek H and Janipalli, Charles S and Mani, K Radha and Yajnik, Chittaranjan S and Hofman, Albert and Mattace-Raso, Francesco U S and Oostra, Ben A and Demirkan, Ayse and Isaacs, Aaron and Rivadeneira, Fernando and Lakatta, Edward G and Orr{\`u}, Marco and Scuteri, Angelo and Ala-Korpela, Mika and Kangas, Antti J and Lyytik{\"a}inen, Leo-Pekka and Soininen, Pasi and Tukiainen, Taru and W{\"u}rtz, Peter and Ong, Rick Twee-Hee and D{\"o}rr, Marcus and Kroemer, Heyo K and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Galan, Pilar and Hercberg, Serge and Lathrop, Mark and Zelenika, Diana and Deloukas, Panos and Mangino, Massimo and Spector, Tim D and Zhai, Guangju and Meschia, James F and Nalls, Michael A and Sharma, Pankaj and Terzic, Janos and Kumar, M V Kranthi and Denniff, Matthew and Zukowska-Szczechowska, Ewa and Wagenknecht, Lynne E and Fowkes, F Gerald R and Charchar, Fadi J and Schwarz, Peter E H and Hayward, Caroline and Guo, Xiuqing and Rotimi, Charles and Bots, Michiel L and Brand, Eva and Samani, Nilesh J and Polasek, Ozren and Talmud, Philippa J and Nyberg, Fredrik and Kuh, Diana and Laan, Maris and Hveem, Kristian and Palmer, Lyle J and van der Schouw, Yvonne T and Casas, Juan P and Mohlke, Karen L and Vineis, Paolo and Raitakari, Olli and Ganesh, Santhi K and Wong, Tien Y and Tai, E Shyong and Cooper, Richard S and Laakso, Markku and Rao, Dabeeru C and Harris, Tamara B and Morris, Richard W and Dominiczak, Anna F and Kivimaki, Mika and Marmot, Michael G and Miki, Tetsuro and Saleheen, Danish and Chandak, Giriraj R and Coresh, Josef and Navis, Gerjan and Salomaa, Veikko and Han, Bok-Ghee and Zhu, Xiaofeng and Kooner, Jaspal S and Melander, Olle and Ridker, Paul M and Bandinelli, Stefania and Gyllensten, Ulf B and Wright, Alan F and Wilson, James F and Ferrucci, Luigi and Farrall, Martin and Tuomilehto, Jaakko and Pramstaller, Peter P and Elosua, Roberto and Soranzo, Nicole and Sijbrands, Eric J G and Altshuler, David and Loos, Ruth J F and Shuldiner, Alan R and Gieger, Christian and Meneton, Pierre and Uitterlinden, Andr{\'e} G and Wareham, Nicholas J and Gudnason, Vilmundur and Rotter, Jerome I and Rettig, Rainer and Uda, Manuela and Strachan, David P and Witteman, Jacqueline C M and Hartikainen, Anna-Liisa and Beckmann, Jacques S and Boerwinkle, Eric and Vasan, Ramachandran S and Boehnke, Michael and Larson, Martin G and Jarvelin, Marjo-Riitta and Psaty, Bruce M and Abecasis, Goncalo R and Chakravarti, Aravinda and Elliott, Paul and van Duijn, Cornelia M and Newton-Cheh, Christopher and Levy, Daniel and Caulfield, Mark J and Johnson, Toby} } @article {7569, title = {New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.}, journal = {Circ Cardiovasc Genet}, volume = {10}, year = {2017}, month = {2017 Oct}, abstract = {

BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.

METHODS AND RESULTS: Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5{\texttimes}10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.

CONCLUSIONS: We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.117.001778}, author = {Kraja, Aldi T and Cook, James P and Warren, Helen R and Surendran, Praveen and Liu, Chunyu and Evangelou, Evangelos and Manning, Alisa K and Grarup, Niels and Drenos, Fotios and Sim, Xueling and Smith, Albert Vernon and Amin, Najaf and Blakemore, Alexandra I F and Bork-Jensen, Jette and Brandslund, Ivan and Farmaki, Aliki-Eleni and Fava, Cristiano and Ferreira, Teresa and Herzig, Karl-Heinz and Giri, Ayush and Giulianini, Franco and Grove, Megan L and Guo, Xiuqing and Harris, Sarah E and Have, Christian T and Havulinna, Aki S and Zhang, He and J{\o}rgensen, Marit E and K{\"a}r{\"a}j{\"a}m{\"a}ki, AnneMari and Kooperberg, Charles and Linneberg, Allan and Little, Louis and Liu, Yongmei and Bonnycastle, Lori L and Lu, Yingchang and M{\"a}gi, Reedik and Mahajan, Anubha and Malerba, Giovanni and Marioni, Riccardo E and Mei, Hao and Menni, Cristina and Morrison, Alanna C and Padmanabhan, Sandosh and Palmas, Walter and Poveda, Alaitz and Rauramaa, Rainer and Rayner, Nigel William and Riaz, Muhammad and Rice, Ken and Richard, Melissa A and Smith, Jennifer A and Southam, Lorraine and Stan{\v c}{\'a}kov{\'a}, Alena and Stirrups, Kathleen E and Tragante, Vinicius and Tuomi, Tiinamaija and Tzoulaki, Ioanna and Varga, Tibor V and Weiss, Stefan and Yiorkas, Andrianos M and Young, Robin and Zhang, Weihua and Barnes, Michael R and Cabrera, Claudia P and Gao, He and Boehnke, Michael and Boerwinkle, Eric and Chambers, John C and Connell, John M and Christensen, Cramer K and de Boer, Rudolf A and Deary, Ian J and Dedoussis, George and Deloukas, Panos and Dominiczak, Anna F and D{\"o}rr, Marcus and Joehanes, Roby and Edwards, Todd L and Esko, T{\~o}nu and Fornage, Myriam and Franceschini, Nora and Franks, Paul W and Gambaro, Giovanni and Groop, Leif and Hallmans, G{\"o}ran and Hansen, Torben and Hayward, Caroline and Heikki, Oksa and Ingelsson, Erik and Tuomilehto, Jaakko and Jarvelin, Marjo-Riitta and Kardia, Sharon L R and Karpe, Fredrik and Kooner, Jaspal S and Lakka, Timo A and Langenberg, Claudia and Lind, Lars and Loos, Ruth J F and Laakso, Markku and McCarthy, Mark I and Melander, Olle and Mohlke, Karen L and Morris, Andrew P and Palmer, Colin N A and Pedersen, Oluf and Polasek, Ozren and Poulter, Neil R and Province, Michael A and Psaty, Bruce M and Ridker, Paul M and Rotter, Jerome I and Rudan, Igor and Salomaa, Veikko and Samani, Nilesh J and Sever, Peter J and Skaaby, Tea and Stafford, Jeanette M and Starr, John M and van der Harst, Pim and van der Meer, Peter and van Duijn, Cornelia M and Vergnaud, Anne-Claire and Gudnason, Vilmundur and Wareham, Nicholas J and Wilson, James G and Willer, Cristen J and Witte, Daniel R and Zeggini, Eleftheria and Saleheen, Danish and Butterworth, Adam S and Danesh, John and Asselbergs, Folkert W and Wain, Louise V and Ehret, Georg B and Chasman, Daniel I and Caulfield, Mark J and Elliott, Paul and Lindgren, Cecilia M and Levy, Daniel and Newton-Cheh, Christopher and Munroe, Patricia B and Howson, Joanna M M} } @article {7913, title = {GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 12 03}, pages = {5141}, abstract = {

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

}, keywords = {ADAMTS9 Protein, Amino Acid Oxidoreductases, Carotid Intima-Media Thickness, Coronary Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lod Score, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors}, issn = {2041-1723}, doi = {10.1038/s41467-018-07340-5}, author = {Franceschini, Nora and Giambartolomei, Claudia and de Vries, Paul S and Finan, Chris and Bis, Joshua C and Huntley, Rachael P and Lovering, Ruth C and Tajuddin, Salman M and Winkler, Thomas W and Graff, Misa and Kavousi, Maryam and Dale, Caroline and Smith, Albert V and Hofer, Edith and van Leeuwen, Elisabeth M and Nolte, Ilja M and Lu, Lingyi and Scholz, Markus and Sargurupremraj, Muralidharan and Pitk{\"a}nen, Niina and Franz{\'e}n, Oscar and Joshi, Peter K and Noordam, Raymond and Marioni, Riccardo E and Hwang, Shih-Jen and Musani, Solomon K and Schminke, Ulf and Palmas, Walter and Isaacs, Aaron and Correa, Adolfo and Zonderman, Alan B and Hofman, Albert and Teumer, Alexander and Cox, Amanda J and Uitterlinden, Andr{\'e} G and Wong, Andrew and Smit, Andries J and Newman, Anne B and Britton, Annie and Ruusalepp, Arno and Sennblad, Bengt and Hedblad, Bo and Pasaniuc, Bogdan and Penninx, Brenda W and Langefeld, Carl D and Wassel, Christina L and Tzourio, Christophe and Fava, Cristiano and Baldassarre, Damiano and O{\textquoteright}Leary, Daniel H and Teupser, Daniel and Kuh, Diana and Tremoli, Elena and Mannarino, Elmo and Grossi, Enzo and Boerwinkle, Eric and Schadt, Eric E and Ingelsson, Erik and Veglia, Fabrizio and Rivadeneira, Fernando and Beutner, Frank and Chauhan, Ganesh and Heiss, Gerardo and Snieder, Harold and Campbell, Harry and V{\"o}lzke, Henry and Markus, Hugh S and Deary, Ian J and Jukema, J Wouter and de Graaf, Jacqueline and Price, Jacqueline and Pott, Janne and Hopewell, Jemma C and Liang, Jingjing and Thiery, Joachim and Engmann, Jorgen and Gertow, Karl and Rice, Kenneth and Taylor, Kent D and Dhana, Klodian and Kiemeney, Lambertus A L M and Lind, Lars and Raffield, Laura M and Launer, Lenore J and Holdt, Lesca M and D{\"o}rr, Marcus and Dichgans, Martin and Traylor, Matthew and Sitzer, Matthias and Kumari, Meena and Kivimaki, Mika and Nalls, Mike A and Melander, Olle and Raitakari, Olli and Franco, Oscar H and Rueda-Ochoa, Oscar L and Roussos, Panos and Whincup, Peter H and Amouyel, Philippe and Giral, Philippe and Anugu, Pramod and Wong, Quenna and Malik, Rainer and Rauramaa, Rainer and Burkhardt, Ralph and Hardy, Rebecca and Schmidt, Reinhold and de Mutsert, Ren{\'e}e and Morris, Richard W and Strawbridge, Rona J and Wannamethee, S Goya and H{\"a}gg, Sara and Shah, Sonia and McLachlan, Stela and Trompet, Stella and Seshadri, Sudha and Kurl, Sudhir and Heckbert, Susan R and Ring, Susan and Harris, Tamara B and Lehtim{\"a}ki, Terho and Galesloot, Tessel E and Shah, Tina and de Faire, Ulf and Plagnol, Vincent and Rosamond, Wayne D and Post, Wendy and Zhu, Xiaofeng and Zhang, Xiaoling and Guo, Xiuqing and Saba, Yasaman and Dehghan, Abbas and Seldenrijk, Adrie and Morrison, Alanna C and Hamsten, Anders and Psaty, Bruce M and van Duijn, Cornelia M and Lawlor, Deborah A and Mook-Kanamori, Dennis O and Bowden, Donald W and Schmidt, Helena and Wilson, James F and Wilson, James G and Rotter, Jerome I and Wardlaw, Joanna M and Deanfield, John and Halcox, Julian and Lyytik{\"a}inen, Leo-Pekka and Loeffler, Markus and Evans, Michele K and Debette, Stephanie and Humphries, Steve E and V{\"o}lker, Uwe and Gudnason, Vilmundur and Hingorani, Aroon D and Bj{\"o}rkegren, Johan L M and Casas, Juan P and O{\textquoteright}Donnell, Christopher J} }