790 results on '"Samani, NJ"'
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2. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
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Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, AV, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Velez Edwards, DR, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, De Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, I, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, YV, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, AI, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Davey Smith, G, Boer, RAD, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, Van der Harst, P, Van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, DI, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, and United Kingdom Research and Innovation
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Genetics & Heredity ,Understanding Society Scientific Group ,Science & Technology ,business.industry ,Published Erratum ,Million Veteran Program ,MEDLINE ,Computational biology ,06 Biological Sciences ,Biology ,Blood pressure ,Text mining ,Meta-analysis ,EPIC-InterAct ,Genetics ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,business ,Life Sciences & Biomedicine ,EPIC-CVD ,11 Medical and Health Sciences ,LifeLines Cohort Study ,Developmental Biology - Abstract
In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article.
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- 2021
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3. Genetic predisposition to coronary artery disease in type 2 diabetes
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van Zuydam, NR, Ladenvall, C, Voight, BF, Strawbridge, RJ, Fernandez Tajes, J, Rayner, NW, Robertson, NR, Mahajan, A, Vlachopoulou, E, Goel, A, Kleber, ME, Nelson, CP, Kwee, LC, Esko, T, Mihailov, E, Mägi, R, Milani, L, Fischer, K, Kanoni, S, Kumar, J, Song, C, Hartiala, JA, Pedersen, NL, Perola, M, Gieger, C, Peters, A, Qu, L, Willems, SM, Doney, ASF, Morris, AD, Zheng, Y, Sesti, G, Hu, FB, Qi, L, Laakso, M, Thorsteinsdottir, U, Grallert, H, van Duijn, C, Reilly, MP, Ingelsson, E, Deloukas, P, Kathiresan, S, Metspalu, A, Shah, SH, Sinisalo, J, Salomaa, V, Hamsten, A, Samani, NJ, März, W, Hazen, SL, and Watkins, H
- Abstract
Background - Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes (T2D). Methods - To test whether this reflects differential genetic influences on CAD-risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66,643 subjects (27,708 with CAD and 24,259 with T2D). Variants showing apparent association with CAD in stratified analyses and/or evidence of interaction were evaluated in a further 117,787 subjects (16,694 with CAD and 11,537 with T2D). Results - None of the previously characterised CAD loci was found to have specific effects on CAD in T2D individuals and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions - This study found no evidence that the genetic architecture of CAD differs in those with T2D compared to those without T2D.
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- 2020
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4. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
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Erzurumluoglu, AM, Liu, M, Jackson, VE, Barnes, DR, Datta, G, Melbourne, CA, Young, R, Batini, C, Surendran, P, Jiang, T, Adnan, SD, Afaq, S, Agrawal, A, Altmaier, E, Antoniou, AC, Asselbergs, FW, Baumbach, C, Beirut, L, Bertelsen, S, Boehnke, M, Bots, ML, Brazel, DM, Chambers, JC, Chang-Claude, J, Chen, C, Corley, J, Chou, Y-L, David, SP, de Boer, RA, de Leeuw, CA, Dennis, JG, Dominiczak, AF, Dunning, AM, Easton, DF, Eaton, C, Elliott, P, Evangelou, E, Faul, JD, Foroud, T, Goate, A, Gong, J, Grabe, HJ, Haessler, J, Haiman, C, Hallmans, G, Hammerschlag, AR, Harris, SE, Hattersley, A, Heath, A, Hsu, C, Iacono, WG, Kanoni, S, Kapoor, M, Kaprio, J, Kardia, SL, Karpe, F, Kontto, J, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Laakso, M, Lai, D, Langenberg, C, Le, N, Lettre, G, Loukola, A, Luan, J, Madden, PAF, Mangino, M, Marioni, RE, Marouli, E, Marten, J, Martin, NG, McGue, M, Michailidou, K, Mihailov, E, Moayyeri, A, Moitry, M, Müller-Nurasyid, M, Naheed, A, Nauck, M, Neville, MJ, Nielsen, SF, North, K, Perola, M, Pharoah, PDP, Pistis, G, Polderman, TJ, Posthuma, D, Poulter, N, Qaiser, B, Rasheed, A, Reiner, A, Renström, F, Rice, J, Rohde, R, Rolandsson, O, Samani, NJ, Samuel, M, Schlessinger, D, Scholte, SH, Scott, RA, Sever, P, Shao, Y, Shrine, N, Smith, JA, Starr, JM, Stirrups, K, Stram, D, Stringham, HM, Tachmazidou, I, Tardif, J-C, Thompson, DJ, Tindle, HA, Tragante, V, Trompet, S, Turcot, V, Tyrrell, J, Vaartjes, I, van der Leij, AR, van der Meer, P, Varga, TV, Verweij, N, Völzke, H, Wareham, NJ, Warren, HR, Weir, DR, Weiss, S, Wetherill, L, Yaghootkar, H, Yavas, E, Jiang, Y, Chen, F, Zhan, X, Zhang, W, Zhao, W, Zhou, K, Amouyel, P, Blankenberg, S, Caulfield, MJ, Chowdhury, R, Cucca, F, Deary, IJ, Deloukas, P, Di Angelantonio, E, Ferrario, M, Ferrières, J, Franks, PW, Frayling, TM, Frossard, P, Hall, IP, Hayward, C, Jansson, J-H, Jukema, JW, Kee, F, Männistö, S, Metspalu, A, Munroe, PB, Nordestgaard, BG, Palmer, CNA, Salomaa, V, Sattar, N, Spector, T, Strachan, DP, Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ Consortium, van der Harst, P, Zeggini, E, Saleheen, D, Butterworth, AS, Wain, LV, Abecasis, GR, Danesh, J, Tobin, MD, Vrieze, S, Liu, DJ, and Howson, JMM
- Abstract
Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P
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- 2020
5. Enrichment of Rare Variants in Loeys-Dietz Syndrome Genes in Spontaneous Coronary Artery Dissection but Not in Severe Fibromuscular Dysplasia
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Verstraeten, A, Perik, MHAM, Baranowska, AA, Meester, JAN, Van Den Heuvel, L, Bastianen, J, Kempers, M, Krapels, IPC, Maas, A, Rideout, A, Vandersteen, A, Sobey, G, JOHNSON, D, Fransen, E, Ghali, N, Webb, T, Al-Hussaini, A, de Leeuw, P, Delmotte, P, Lopez-Sublet, M, Pappaccogli, M, Sprynger, M, Toubiana, L, European/International Fibromuscular Dysplasia Registry and Initiative, (FEIRI), Van Laer, L, Van Dijk, FS, Vikkula, M, Samani, NJ, Persu, A, Adlam, D, Loeys, B, Collaborators of the European/International Fibromuscular Dysplasia Registry and Initiative, (FEIRI), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), and Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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fibromuscular dysplasia ,genetics ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Loeys-Dietz syndrome ,coronary artery disease - Published
- 2020
6. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
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Landi MT, Bishop DT, MacGregor S, Machiela MJ, Stratigos AJ, Ghiorzo P, Brossard M, Calista D, Choi J, Fargnoli MC, Zhang T, Rodolfo M, Trower AJ, Menin C, Martinez J, Hadjisavvas A, Song L, Stefanaki I, Scolyer R, Yang R, Goldstein AM, Potrony M, Kypreou KP, Pastorino L, Queirolo P, Pellegrini C, Cattaneo L, Zawistowski M, Gimenez-Xavier P, Rodriguez A, Elefanti L, Manoukian S, Rivoltini L, Smith BH, Loizidou MA, Del Regno L, Massi D, Mandala M, Khosrotehrani K, Akslen LA, Amos CI, Andresen PA, Avril MF, Azizi E, Soyer HP, Bataille V, Dalmasso B, Bowdler LM, Burdon KP, Chen WV, Codd V, Craig JE, Debniak T, Falchi M, Fang S, Friedman E, Simi S, Galan P, Garcia-Casado Z, Gillanders EM, Gordon S, Green A, Gruis NA, Hansson J, Harland M, Harris J, Helsing P, Henders A, Hocevar M, Höiom V, Hunter D, Ingvar C, Kumar R, Lang J, Lathrop GM, Lee JE, Li X, Lubinski J, Mackie RM, Malt M, Malvehy J, McAloney K, Mohamdi H, Molven A, Moses EK, Neale RE, Novakovic S, Nyholt DR, Olsson H, Orr N, Fritsche LG, Puig-Butille JA, Qureshi AA, Radford-Smith GL, Randerson-Moor J, Requena C, Rowe C, Samani NJ, Sanna M, Schadendorf D, Schulze HJ, Simms LA, Smithers M, Song F, Swerdlow AJ, van der Stoep N, Kukutsch NA, Visconti A, Wallace L, Ward SV, Wheeler L, Sturm RA, Hutchinson A, Jones K, Malasky M, Vogt A, Zhou W, Pooley KA, Elder DE, Han J, Hicks B, Hayward NK, Kanetsky PA, Brummett C, Montgomery GW, Olsen CM, Hayward C, Dunning AM, Martin NG, Evangelou E, Mann GJ, Long G, Pharoah PDP, Easton DF, Barrett JH, Cust AE, Abecasis G, Duffy DL, Whiteman DC, Gogas H, De Nicolo A, Tucker MA, Newton-Bishop JA, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, SDH Study Group, IBD Investigators, Essen-Heidelberg Investigators, AMFS Investigators, MelaNostrum Consortium, Peris K, Chanock SJ, Demenais F, Brown KM, Puig S, Nagore E, Shi J, Iles MM, and Law MH
- Abstract
Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma. Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
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- 2020
7. Defining the role of common variation in the genomic and biological architecture of adult human height
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Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, 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Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
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Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,Medizin ,Genome-wide association study ,Adult ,Analysis of Variance ,Body Height/genetics ,European Continental Ancestry Group/genetics ,Genetic Variation/genetics ,Genetics, Population ,Genome-Wide Association Study/methods ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism, Single Nucleotide/genetics ,heritability ,0302 clinical medicine ,Genome-wide ,SNPS ,snps ,Genetics & Heredity ,ddc:616 ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,variants ,GENETIC-VARIATION ,Biological Sciences ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,body height ,genetic-variation ,Life Sciences & Biomedicine ,Single Nucleotide/genetics ,Human ,European Continental Ancestry Group ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,NO ,complex traits ,03 medical and health sciences ,Genetic variation ,heritability, adult, height ,Polymorphism ,Human height ,PAGEGE Consortium ,education ,Gene ,VLAG ,030304 developmental biology ,Global Nutrition ,Wereldvoeding ,genome-wide association study ,Science & Technology ,Whites ,Oligonucleotide Array Sequence Analysi ,MUTATIONS ,COMPLEX TRAITS ,ta1184 ,Klinisk medicin ,population genetics ,Genetic Variation ,Heritability ,ta3121 ,mutations ,Genetic architecture ,Body Height ,genetic variation ,MIGen Consortium ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Clinical Medicine ,030217 neurology & neurosurgery ,height ,LifeLines Cohort Study ,Developmental Biology ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
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- View/download PDF
8. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events
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Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW
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Male ,Myocardial Infarction ,genetic risk factor ,Coronary Artery Disease ,Middle Aged ,Article ,chromosome 9p21 ,Gene Frequency ,Risk Factors ,Case-Control Studies ,Odds Ratio ,Humans ,Female ,Genetic Predisposition to Disease ,cardiovascular diseases ,Chromosomes, Human, Pair 9 ,secondary prevention - Abstract
Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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- 2019
9. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)
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Evangelou, E, Warren, HR, Mosen-Ansorena, D, Mifsud, B, Pazoki, R, Gao, H, Ntritsos, G, Dimou, N, Cabrera, CP, Karaman, I, Fu, LN, Evangelou, M, Witkowska, K, Tzanis, E, Hellwege, JN, Giri, A, Edwards, DRV, Sun, YV, Cho, K, Gaziano, JM, Wilson, PWF, Tsao, PS, Kovesdy, CP, Esko, T, Magi, R, Milani, L, Almgren, P, Boutin, T, Debette, S, Ding, J, Giulianini, F, Holliday, EG, Jackson, AU, Li-Gao, R, Lin, W-Y, Luan, J, Mangino, M, Oldmeadow, C, Prins, BP, Qian, Y, Sargurupremraj, M, Shah, N, Surendran, P, Theriault, S, Verweij, N, Willems, SM, Zhao, J-H, Amouyel, P, Connell, J, De Mutsert, R, Doney, ASF, Farrall, M, Menni, C, Morris, AD, Noordam, R, Pare, G, Poulter, NR, Shields, DC, Stanton, A, Thom, S, Abecasis, G, Amin, N, Arking, DE, Ayers, KL, Barbieri, CM, Batini, C, Bis, JC, Blake, T, Bochud, M, Boehnke, M, Boerwinkle, E, Boomsma, DI, Bottinger, EP, Braund, PS, Brumat, M, Campbell, A, Campbell, H, Chakravarti, A, Chambers, JC, Chauhan, G, Ciullo, M, Cocca, M, Collins, F, Cordell, HJ, Davies, G, De Borst, MH, De Geus, EJ, Deary, IJ, Deelen, J, Del Greco, FM, Demirkale, CY, Dorr, M, Ehret, GB, Elosua, R, Enroth, S, Erzurumluoglu, AM, Ferreira, T, Franberg, M, Franco, OH, Gandin, I, Gasparini, P, Giedraitis, V, Gieger, C, Girotto, G, Goel, A, Gow, AJ, Gudnason, V, Guo, X, Gyllensten, U, Hamsten, A, Harris, TB, Harris, SE, Hartman, CA, Havulinna, AS, Hicks, AA, Hofer, E, Hofman, A, Hottenga, J-J, Huffman, JE, Hwang, S-J, Ingelsson, E, James, A, Jansen, R, Jarvelin, M-R, Joehanes, R, Johansson, A, Johnson, AD, Joshi, PK, Jousilahti, P, Jukema, JW, Jula, A, Kahonen, M, Kathiresan, S, Keavney, BD, Khaw, K-T, Knekt, P, Knight, J, Kolcic, I, Kooner, JS, Koskinen, S, Kristiansson, K, Kutalik, Z, Laan, M, Larson, M, Launer, LJ, Lehne, B, Lehtimaki, T, Liewald, DCM, Lin, L, Lind, L, Lindgren, CM, Liu, Y, Loos, RJF, Lopez, LM, Lu, Y, Lyytikainen, L-P, Mahajan, A, Mamasoula, C, Marrugat, J, Marten, J, Milaneschi, Y, Morgan, A, Morris, AP, Morrison, AC, Munson, PJ, Nalls, MA, Nandakumar, P, Nelson, CP, Niiranen, T, Nolte, IM, Nutile, T, Oldehinkel, AJ, Oostra, BA, O'Reilly, PF, Org, E, Padmanabhan, S, Palmas, W, Palotie, A, Pattie, A, Penninx, BWJH, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Quang, TN, Raitakari, OT, Ren, M, Rettig, R, Rice, K, Ridker, PM, Ried, JS, Riese, H, Ripatti, S, Robino, A, Rose, LM, Rotter, JI, Rudan, I, Ruggiero, D, Saba, Y, Sala, CF, Salomaa, V, Samani, NJ, Sarin, A-P, Schmidt, R, Schmidt, H, Shrine, N, Siscovick, D, Smith, AV, Snieder, H, Sober, S, Sorice, R, Starr, JM, Stott, DJ, Strachan, DP, Strawbridge, RJ, Sundstrom, J, Swertz, MA, Taylor, KD, Teumer, A, Tobin, MD, Tomaszewski, M, Toniolo, D, Traglia, M, Trompet, S, Tuomilehto, J, Tzourio, C, Uitterlinden, AG, Vaez, A, Van der Most, PJ, Van Duijn, CM, Vergnaud, A-C, Verwoert, GC, Vitart, V, Volker, U, Vollenweider, P, Vuckovic, D, Watkins, H, Wild, SH, Willemsen, G, Wilson, JF, Wright, AF, Yao, J, Zemunik, T, Zhang, W, Attia, JR, Butterworth, AS, Chasman, DI, Conen, D, Cucca, F, Danesh, J, Hayward, C, Howson, JMM, Laakso, M, Lakatta, EG, Langenberg, C, Melander, O, Mook-Kanamori, DO, Palmer, CNA, Risch, L, Scott, RA, Scott, RJ, Sever, P, Spector, TD, Van der Harst, P, Wareham, NJ, Zeggini, E, Levy, D, Munroe, PB, Newton-Cheh, C, Brown, MJ, Metspalu, A, Hung, AM, O'Donnell, CJ, Edwards, TL, Psaty, BM, Tzoulaki, I, Barnes, MR, Wain, LV, Elliott, P, and Caulfield, MJ
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Genetics & Heredity ,Science & Technology ,Million Veteran Program ,06 Biological Sciences ,Life Sciences & Biomedicine ,11 Medical and Health Sciences ,Developmental Biology - Abstract
Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.
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- 2018
10. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)
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Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
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- 2018
11. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)
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Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, 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Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
- Published
- 2018
12. MAPPING OF QUANTITATIVE TRAIT LOCI INFLUENCING RELATIVE LEFT VENTRICULAR MASS IN GENETIC HYPERTENSION
- Author
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Samani, NJ, Rattray, F, Kaiser, M, and Vincent, M
- Published
- 1998
13. DEMONSTRATION OF IMPAIRED MYOCARDIAL PERFUSION RESERVE IN PATIENTS WITH SYNDROME X USING MAGNETIC RESONANCE IMAGING
- Author
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Cullen, JHS, Horsfield, Reek, CR, Barnett, DB, Cherryman, GR, and Samani, NJ
- Published
- 1998
14. QUANTITATIVE ESTIMATION OF MYOCARDIAL PERFUSION RESERVE IN HUMANS USING FIRST-PASS CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING
- Author
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Cullen, JHS, Samani, NJ, Horsfield, Reek, CR, Barnett, DB, and Cherryman, GR
- Published
- 1998
15. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
- Author
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Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. 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C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van Duijn, Cornelia M. 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Linsel-Nitschke P, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Wallace C, Kathiresan S, Reilly MP, Erdmann J, Assimes TL, Boerwinkle E, Hall A, König IR, Laaksonen R, McPherson R, Thompson JR, Thorsteinsdottir U, Ziegler A, Absher D, Chen L, Cupples LA, Halperin E, Li M, Musunuru K, Preuss M, Schillert A, Thorleifsson G, Voight BF, Wells GA, Assime TL, Holm H, Roberts R, Stewart AF, Fortmann S, Go A, Hlatky M, Iribarren C, Knowles J, Myers R, Quertermous T, Sidney S, Risch N, Tang H, Blankenberg S, Zeller T, Wild P, Schnabel R, Sinning C, Lackner K, Tiret L, Nicaud V, Bickel C, Rupprecht HJ, Perret C, Proust C, Münzel T, Barbalic M, Bis J, Chen IY, Cupples L, Demissie-Banjaw S, Folsom A, Glazer N, Harris T, Heckbert S, Lumley T, Marciante K, Morrison A, O' Donnell CJ, Psaty BM, Rice K, Rotter JI, Siscovick DS, Smith N, Smith A, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Uitterlinden A, Gretarsdottir S, Gulcher JR, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Fischer M, Grosshennig A, Lieb W, Stark K, Schreiber S, Wichmann HE, Aherrahrou Z, Bruse P, Doering A, Illig T, Klopp N, Loley C, Medack A, Meisinger C, Meitinger T, Nahrstedt J, Peters A, Wagner AK, Willenborg C, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, März W, Meinitzer A, Winkelmann BR, Pilz S, Renner W, Scharnagl H, Stojakovic T, Tomaschitz A, Winkler K, Guiducci C, Burtt N, Gabriel SB, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Dandona S, Jarinova O, Qu L, Wilensky R, Matthai W, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Yang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Willerson JT, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Gao X, Yang Q, O'Connell JR, Schmidt H, Ketkar S, Hwang SJ, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Siscovick D, Zillikens MC, Feitosa M, Province M, de Andrade M, Turner ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. G., Sijbrand, Andre G., Uitterlinden, Shih Jen, Hwang, Ramachandran S., Vasan, Thomas J., Wang, Sven, Bergmann, Peter, Vollenweider, Gérard, Waeber, Jaana, Laitinen, Anneli, Pouta, Paavo, Zitting, Wendy L., Mcardle, Heyo K., Kroemer, Uwe, Völker, Henry, Völzke, Nicole L., Glazer, Kent D., Taylor, Tamara B., Harri, Helene, Alavere, Toomas, Haller, Aime, Kei, Mari Liis, Tammesoo, Yurii, Aulchenko, Inês, Barroso, Kay Tee, Khaw, Pilar, Galan, Serge, Hercberg, Mark, Lathrop, Susana, Eyheramendy, Elin, Org, Siim, Sõber, Xiaowen, Lu, Ilja M., Nolte, Brenda W., Penninx, Tanguy, Corre, Corrado, Masciullo, Cinzia, Sala, Leif, Groop, Benjamin F., Voight, Olle, Melander, Christopher J., O'Donnell, Veikko, Salomaa, D'Adamo, ADAMO PIO, Antonella, Fabretto, Flavio, Faletra, Sheila, Ulivi, Fabiola Del Greco, M, Maurizio, Facheri, Francis S., Collin, Richard N., Bergman, John P., Beilby, Joseph, Hung, A., William Musk, Massimo, Mangino, So Youn, Shin, Nicole, Soranzo, Hugh, Watkin, Anuj, Goel, Anders, Hamsten, Pierre, Gider, Marisa, Loitfelder, Marion, Zeginigg, Dena, Hernandez, Samer S., Najjar, Pau, Navarro, Sarah H., Wild, Anna Maria, Corsi, Andrew, Singleton, Eco J. C., de Geu, Gonneke, Willemsen, Alex N., Parker, Lynda M., Rose, Brendan, Buckley, David, Stott, Marco, Orru, Manuela, Uda, Melanie M., van der Klauw, Weihua, Zhang, Xinzhong, Li, James, Scott, Yii Der Ida, Chen, Gregory L., Burke, Mika, Kähönen, Jorma, Viikari, Angela, Döring, Thomas, Meitinger, Gail, Davie, John M., Starr, Valur, Emilsson, Andrew, Plump, Jan H., Lindeman, Peter A. C., 't Hoen, Inke R., König, Janine F., Felix, Robert, Clarke, Jemma C., Hopewell, Halit, Ongen, Monique, Breteler, Stéphanie, Debette, Anita L., Destefano, Myriam, Fornage, Gary F., Mitchell, Nicholas L., Smith, Hilma, Holm, Kari, Stefansson, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Nilesh J., Samani, Michael, Preu, Igor, Rudan, Caroline, Hayward, Ian J., Deary, H., Erich Wichmann, Olli T., Raitakari, Walter, Palma, Jaspal S., Kooner, Ronald P., Stolk, J., Wouter Jukema, Alan F., Wright, Dorret I., Boomsma, Stefania, Bandinelli, Ulf B., Gyllensten, James F., Wilson, Luigi, Ferrucci, Reinhold, Schmidt, Martin, Farrall, Tim D., Spector, Lyle J., Palmer, Jaakko, Tuomilehto, Arne, Pfeufer, Gasparini, Paolo, David, Siscovick, David, Altshuler, Ruth J. F., Loo, Daniela, Toniolo, Harold, Snieder, Christian, Gieger, Pierre, Meneton, Nicholas J., Wareham, Ben A., Oostra, Andres, Metspalu, Lenore, Launer, Rainer, Rettig, David P., Strachan, Jacques S., Beckmann, Jacqueline C. M., Witteman, Jeanette, Erdmann, Ko Willems van, Dijk, Eric, Boerwinkle, Michael, Boehnke, Paul M., Ridker, Marjo Riitta, Jarvelin, Aravinda, Chakravarti, Goncalo R., Abecasi, Vilmundur, Gudnason, Christopher Newton, Cheh, Daniel, Levy, Patricia B., Munroe, Bruce M., Psaty, Mark J., Caulfield, Dabeeru C., Rao, Martin D., Tobin, Paul, Elliott, Cornelia M., van Duijn, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcu, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Mari, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, Mcardle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Tooma, Keis, Aime, Tammesoo, Mari-Lii, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Ander, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, Jame, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thoma, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andre, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willem, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van, Duijn, Cornelia M., McEniery CM, Wilkinson, Ib, Cockcroft, Jr, O'Shaughnessy, Km, Newhouse, Sj, Yasmin, Smith, Av, Eiriksdottir, G, Launer, Lj, Sigurdsson, S, Aspelund, T, Gudnason, V, De Bacquer, D, Rietzschel, Er, De Backer, Gg, Van Bortel, L, De Buyzere, Ml, Segers, P, Bekaert, S, Gillebert, Tc, De Meyer, T, Ferrucci, L, Tanaka, T, Johnson, Ad, Levy, D, Benjamin, Ej, Mitchell, Gf, Vita, Ja, Larson, Mg, Hamburg, Nm, Vasan, R, Isaacs, A, Schut, Af, Oostra, Ba, van Duijn, Cm, van Rijn, Mj, Sie, Mp, Newman, Ab, Herrington, Dm, Andrews, J, Ding, J, Sutton-Tyrrell, Kc, Harris, Tb, Howard, Td, Liu, Y, Parsa, A, Shuldiner, Ar, Mcardle, Pf, Gibson, Q, Post, W, Dehghan, A, Hofman, A, Uitterlinden, Ag, Sijbrands, Ej, Rivadeneira, F, Mattace-Raso, Fu, Verwoert, Gc, Witteman, Jc, Scuteri, A, Lakatta, Eg, Jewell, E, Abecasis, Gr, Tarasov, Kv, Uda, M, Najjar, S, Sanna, S, Attwood, T, Belz, S, Braund, P, Cambien, F, Cooper, J, Crisp-Hihn, A, Deloukas, P, Foad, N, Eardman, J, Goodall, Ah, Gracey, J, Gray, E, Gulde, S, Gwilliams, R, Heimerl, S, Hengstenberg, C, Jolley, J, Krishnan, U, Linsel-Nitschke, P, Lloyd-Jones, H, Lugauer, I, Lundmark, P, Maouche, S, Moore, J, Muir, D, Murray, E, Nelson, Cp, Neudert, J, Niblett, D, O'Leary, K, Ouwehand, Wh, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Samani, Nj, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Schunkert, H, Syvannen, Ac, Wallace, C, Kathiresan, S, Reilly, Mp, Erdmann, J, Assimes, Tl, Boerwinkle, E, Hall, A, König, Ir, Laaksonen, R, Mcpherson, R, Thompson, Jr, Thorsteinsdottir, U, Ziegler, A, Absher, D, Chen, L, Cupples, La, Halperin, E, Li, M, Musunuru, K, Preuss, M, Schillert, A, Thorleifsson, G, Voight, Bf, Wells, Ga, Assime, Tl, Holm, H, Roberts, R, Stewart, Af, Fortmann, S, Go, A, Hlatky, M, Iribarren, C, Knowles, J, Myers, R, Quertermous, T, Sidney, S, Risch, N, Tang, H, Blankenberg, S, Zeller, T, Wild, P, Schnabel, R, Sinning, C, Lackner, K, Tiret, L, Nicaud, V, Bickel, C, Rupprecht, Hj, Perret, C, Proust, C, Münzel, T, Barbalic, M, Bis, J, Chen, Iy, Cupples, L, Demissie-Banjaw, S, Folsom, A, Glazer, N, Harris, T, Heckbert, S, Lumley, T, Marciante, K, Morrison, A, O' Donnell, Cj, Psaty, Bm, Rice, K, Rotter, Ji, Siscovick, D, Smith, N, Smith, A, Taylor, Kd, van Duijn, C, Volcik, K, Whitteman, J, Ramachandran, V, Uitterlinden, A, Gretarsdottir, S, Gulcher, Jr, Kong, A, Stefansson, K, Thorgeirsson, G, Andersen, K, Fischer, M, Grosshennig, A, Lieb, W, Stark, K, Schreiber, S, Wichmann, He, Aherrahrou, Z, Bruse, P, Doering, A, Illig, T, Klopp, N, Loley, C, Medack, A, Meisinger, C, Meitinger, T, Nahrstedt, J, Peters, A, Wagner, Ak, Willenborg, C, Böhm, Bo, Dobnig, H, Grammer, Tb, Hoffmann, Mm, Kleber, M, März, W, Meinitzer, A, Winkelmann, Br, Pilz, S, Renner, W, Scharnagl, H, Stojakovic, T, Tomaschitz, A, Winkler, K, Guiducci, C, Burtt, N, Gabriel, Sb, O'Donnell, Cj, Elosua, R, Peltonen, L, Salomaa, V, Schwartz, Sm, Melander, O, Altshuler, D, Dandona, S, Jarinova, O, Qu, L, Wilensky, R, Matthai, W, Hakonarson, Hh, Devaney, J, Burnett, M, Pichard, Ad, Kent, Km, Satler, L, Lindsay, Jm, Waksman, R, Knouff, Cw, Waterworth, Dm, Walker, Mc, Mooser, V, Epstein, Se, Rader, Dj, Wright, Bj, Balmforth, Aj, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Yang, Ya, Stricker, Bh, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Willerson, Jt, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Gao, X, Yang, Q, O'Connell, Jr, Schmidt, H, Ketkar, S, Hwang, Sj, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Zillikens, Mc, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Coresh, J, Schmidt, R, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Reffelmann, T, Redfield, Mm, Werdan, K, Arnett, Dk, Blettner, M, Friedrich, N, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Vollenweider, P, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Lightstone, L, Scott, J, Navis, G, Elliott, P, and Kooner, Js.
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Netherlands Twin Register (NTR) ,Linkage disequilibrium ,pulse pressure ,mean arterial pressure ,genome-wide ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,BLOOD-PRESSURE ,Blood Pressure ,030204 cardiovascular system & hematology ,Linkage Disequilibrium ,0302 clinical medicine ,RELEVANCE ,CardioGram ,Medicine and Health Sciences ,Genetics & Heredity ,ddc:616 ,Genetics ,0303 health sciences ,Genome-wide association ,11 Medical And Health Sciences ,Arteries ,ADRENERGIC-RECEPTOR TRAFFICKING ,Pulse pressure ,EchoGen consortium ,Hypertension ,HEART-FAILURE ,arterial pressure ,Case-Control Studie ,Life Sciences & Biomedicine ,Human ,circulatory and respiratory physiology ,medicine.medical_specialty ,Mean arterial pressure ,Arterie ,AortaGen Consortium ,Cardiogenics consortium ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Article ,Follow-Up Studie ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,METAANALYSIS ,030304 developmental biology ,Genetic association ,Science & Technology ,HYPERTENSION ,MORTALITY ,Case-control study ,CARDIOVASCULAR-DISEASE RISK ,06 Biological Sciences ,GENE ,MICE ,Endocrinology ,Blood pressure ,CKDGen consortium ,Genetic Loci ,Case-Control Studies ,KidneyGen consortium ,CHARGE Consortium Heart Failure Working Group ,LifeLines Cohort Study ,Developmental Biology ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). 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 x 10(-8) to P = 2.3 x 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.
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- 2016
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16. The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure: BIOSTAT-CHF Subanalysis
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Bayes-Genis, A, Núñez, J, Zannad, F, Ferreira, JP, Anker, SD, Cleland, JG, Dickstein, K, Filippatos, G, Lang, CC, Ng, LL, Ponikowski, P, Samani, NJ, Van Veldhuisen, DJ, Zwinderman, AH, Metra, M, Lupón, J, and Voors, AA
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Heart Failure ,Male ,Risk ,1102 Cardiovascular Medicine And Haematology ,PCSK9 ,LDLR ,low-density lipoprotein receptor ,proprotein convertase subtilisin/kexin type 9 ,Receptors, LDL ,1117 Public Health And Health Services ,Cardiovascular System & Hematology ,Multivariate Analysis ,Humans ,Prospective Studies ,Proprotein Convertase 9 ,Aged ,Forecasting ,Proportional Hazards Models - Abstract
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES: The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS: The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. RESULTS: This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. CONCLUSIONS: The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
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- 2017
17. Association between telomere length and risk of cancer and non-neoplastic diseases a mendelian randomization study
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Haycock, PC, Burgess, S, Nounu, A, Zheng, J, Okoli, GN, Bowden, J, Wade, KH, Timpson, NJ, Evans, DM, Willeit, P, Aviv, A, Gaunt, TR, Hemani, G, Mangino, M, Ellis, HP, Kurian, KM, Pooley, KA, Eeles, RA, Lee, JE, Fang, S, Chen, WV, Law, MH, Bowdler, LM, Iles, MM, Yang, Q, Worrall, BB, Markus, HS, Hung, RJ, Amos, CI, Spurdle, AB, Thompson, DJ, O'Mara, TA, Wolpin, B, Amundadottir, L, Stolzenberg-Solomon, R, Trichopoulou, A, Onland-Moret, NC, Lund, E, Duell, EJ, Canzian, F, Severi, G, Overvad, K, Gunter, MJ, Tumino, R, Svenson, U, Van Rij, A, Baas, AF, Bown, MJ, Samani, NJ, Van t'Hof, FNG, Tromp, G, Jones, GT, Kuivaniemi, H, Elmore, JR, Johansson, M, Mckay, J, Scelo, G, Carreras-Torres, R, Gaborieau, V, Brennan, P, Bracci, PM, Neale, RE, Olson, SH, Gallinger, S, Li, D, Petersen, GM, Risch, HA, Klein, AP, Han, J, Abnet, CC, Freedman, ND, Taylor, PR, Maris, JM, Aben, KK, Kiemeney, LA, Vermeulen, SH, Wiencke, JK, and Walsh, KM
- Abstract
Copyright 2017 American Medical Association. All rights reserved. IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- 2017
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18. Biological interpretation of genome-wide association studies using predicted gene functions
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Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Chu AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Mägi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AA, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Mateo Leach I, Medina Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Ärnlöv J, Arscott GM, 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Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, van Dijk, S, van Schoor, N, van der Velde, N, van Heemst, D, van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, I, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, de Faire, U, den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Pers, Th, Karjalainen, Jm, Westra, Hj, Wood, Ar, Lui, Jc, Speliotes, Ek, Hirschhorn, Jn, and Faculty of Health Sciences
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Cell type ,Candidate gene ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,LOCI ,General Physics and Astronomy ,Genome-wide association study ,Disease ,Computational biology ,Biology ,Research Support ,General Biochemistry, Genetics and Molecular Biology ,Article ,DISEASE ,N.I.H ,CANDIDATE GENES ,Genome-Wide Association Study/methods ,Software ,HEIGHT ,Research Support, N.I.H., Extramural ,Genetics ,Journal Article ,NETWORK ,Non-U.S. Gov't ,Gene ,COMMON ,Intramural ,ARCHITECTURE ,Biochemistry, Genetics and Molecular Biology (all) ,Multidisciplinary ,IDENTIFICATION ,ta1184 ,Research Support, Non-U.S. Gov't ,Gene sets ,Extramural ,General Chemistry ,ta3121 ,Research Support, N.I.H., Intramural ,Phenotype ,3142 Public health care science, environmental and occupational health ,Biological sciences ,DATA SETS ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Identification (biology) ,INTEGRATION ,Genome-Wide Association Study - Abstract
Article, The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes., published version, http://purl.org/eprint/status/PeerReviewed
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- 2015
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19. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
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Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M
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Linkage disequilibrium ,Multiple Sclerosis ,Genotype ,Population ,Single-nucleotide polymorphism ,Genome-wide association study ,Autoimmunity ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Aminopeptidases ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,Minor Histocompatibility Antigens ,Genetics ,medicine ,Humans ,Spondylitis, Ankylosing ,Receptors, Immunologic ,education ,Genetic association ,education.field_of_study ,Ankylosing spondylitis ,Thyroiditis, Autoimmune ,Chromosome Mapping ,Receptors, Interleukin ,medicine.disease ,Endoplasmic reticulum aminopeptidase 2 ,Genetics, Population ,Haplotypes ,Case-Control Studies ,Immunology ,North America - Abstract
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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- 2016
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20. Large-scale gene-centric analysis identifies novel variants for coronary artery disease
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Butterworth, As, Braund, Ps, Farrall, M, Hardwick, Rj, Saleheen, D, Peden, Jf, Soranzo, N, Chambers, Jc, Sivapalaratnam, S, Kleber, Me, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, Tl, Ball, Sg, Balmforth, Aj, Barnes, Ta, Basart, H, Baumert, J, Bezzina, Cr, Boerwinkle, E, Boehm, Bo, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Cupples, La, de Jong JS, Diemert, P, Ejebe, K, Elbers, Cc, Elliott, P, Fornage, M, Franzosi, Mg, Frossard, P, Garner, S, Goel, A, Goodall, Ah, Hengstenberg, C, Hunt, Se, Kastelein, Jj, Klungel, Oh, Klüter, H, Koch, K, König, Ir, Kooner, As, Laaksonen, R, Lathrop, M, Li, M, Liu, K, Mcpherson, R, Musameh, Md, Musani, S, Nelson, Cp, O'Donnell, Cj, Ongen, H, Papanicolaou, G, Peters, A, Peters, Bj, Potter, S, Psaty, Bm, Qu, L, Rader, Dj, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, Js, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot CE, van der Schouw YT, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, Rs, Wilde, Aa, Willenborg, C, Winkelmann, Br, Zaidi, M, Zhang, W, Ziegler, A, de Bakker PI, Koenig, W, Mätz, W, Trip, Md, Reilly, Mp, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, As, Kooner, Js, Thompson, Sg, Thompson, Jr, Deloukas, P, Ouwehand, Wh, Watkins, H, Danesh, J, Samani, Nj, Barnes, T, Rafelt, S, Bruinsma, N, Dekker, Lr, Henriques, Jp, Koch, Kt, de Winter RJ, Alings, M, Allaart, Cf, Gorgels, Ap, Verheugt, Fw, Mueller, M, Meisinger, C, Derohannessian, S, Mehta, Nn, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, Jc, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Silveira, A, Söderholm, B, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Peden, J, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, Ml, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater Lleal, M, Sennblad, B, Strawbridge, R, Öhrvik, J, Zaman, Ks, Mallick, Nh, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Reilly, M, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, Jl, Ardissino, D, Becker, Lc, Becker, Dm, Berger, K, Bis, Jc, Boekholdt, Sm, Brown, Mj, Burnett, Ms, Buysschaert, I, Carlquist, Jf, Chen, L, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari NE, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, S, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Tennstedt, S, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Musunuru, K, Nahrstaedt, J, Nöthen, Mm, Olivieri, Oliviero, Peyvandi, F, Patel, Rs, Patterson, Cc, Quyyumi, Aa, Rallidis, Ls, Roosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Smith, Av, Smith, Tb, Snoep, Jd, Spertus, Ja, Stefansson, K, Stirrups, K, Stoll, M, Tang, Wh, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Awells, G, Wichmann, He, Witteman, Jc, Wright, Bj, Ye, S, Quertermous, T, März, W, Blankenberg, S, Roberts, R, Onland Moret NC, van Setten, J, Verschuren, Wm, Boer, Jm, Wijmenga, C, Hofker, Mh, Maitland van der Zee AH, de Boer, A, Grobbee, De, Attwood, T, Belz, S, Braund, P, Cooper, J, Crisp Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd Jones, H, Lugauer, I, Lundmark, P, Moore, Js, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, Ac, Wallace, C., Cardiologie, RS: CAPHRI School for Public Health and Primary Care, Vascular Medicine, Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Landsteiner Laboratory, Clinical Haematology, Pulmonology, and Medical Research Council (MRC)
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Male ,Cancer Research ,Candidate gene ,Epidemiology ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Cardiovascular ,0302 clinical medicine ,GENETICS & HEREDITY ,Genetics (clinical) ,Genetics ,0303 health sciences ,Cardiovascular diseases [NCEBP 14] ,Middle Aged ,3. Good health ,CYP17A1 ,Genetic Epidemiology ,Genome-wide association ,Myocardial-infarction ,Susceptibility loci ,Risk ,Atherosclerosis ,Metanalysis ,Lipoprotein ,Medicine ,Female ,Life Sciences & Biomedicine ,Research Article ,Asian Continental Ancestry Group ,Adult ,SUSCEPTIBILITY LOCI ,lcsh:QH426-470 ,European Continental Ancestry Group ,Biology ,Polymorphism, Single Nucleotide ,coronary artery disease ,genetics ,White People ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Asian People ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Allele ,Molecular Biology ,Gene ,METAANALYSIS ,Ecology, Evolution, Behavior and Systematics ,Genetic Association Studies ,Cardiovascular Disease Epidemiology ,Alleles ,030304 developmental biology ,Aged ,0604 Genetics ,Science & Technology ,Case-control study ,Genetic Variation ,Human Genetics ,Odds ratio ,large-scale gene analysis ,lcsh:Genetics ,LIPOPROTEIN ,MYOCARDIAL-INFARCTION ,ATHEROSCLEROSIS ,Case-Control Studies ,Genetics of Disease ,IBC 50K CAD Consortium ,Developmental Biology ,Genome-Wide Association Study - Abstract
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.
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- 2016
21. A positive parental history of high blood pressure
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Samani, NJ
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- 1998
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22. A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site
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Nürnberg ST, Rendon A, Smethurst PA, Paul DS, Voss K, Thon JN, Lloyd Jones H, Sambrook JG, Tijssen MR, Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Mägi R, Meacham S, Okada Y, Sorice R, Teumer A, Zhang W, Ramirez Solis R, Bis JC, Ellinghaus D, Gögele M, Hottenga JJ, Langenberg C, Kovacs P, F. P, Shin SY, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot C, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, Davies G, de Geus EJ, de Boer RA, Döring A, Elliott P, Erdmann J, Feng W, Evans DM, Falchi M, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen AL, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJ, Jolley J, Khaw KT, Kühnel B, Kyrtsonis MC, Lagou V, Lumley T, Mangino M, Maschio A, Mateo Leach I, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nöthlings U, Nakamura Y, Nauck M, Navis G, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Taylor K, Tenesa A, Thein SL, Tönjes A, Uda M, Ulivi S, Wichmann HE, Yang TP, van Veldhuisen DJ, Visscher PM, Völker U, Wiggins KL, Willemsen G, Zhao JH, Zitting P, Bradley JR, Dedoussis GV, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, van Pelt L, Zwaginga JJ, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin MR, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman JW, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Ferreira MA, Italiano JE Jr, Gottgens B, Soranzo N, Ouwehand WH, PIRASTU, Nicola, D'ADAMO, ADAMO PIO, GASPARINI, PAOLO, Nürnberg, St, Rendon, A, Smethurst, Pa, Paul, D, Voss, K, Thon, Jn, Lloyd Jones, H, Sambrook, Jg, Tijssen, Mr, Gieger, C, Radhakrishnan, A, Cvejic, A, Tang, W, Porcu, E, Pistis, G, Serbanovic Canic, J, Elling, U, Goodall, Ah, Labrune, Y, Lopez, Lm, Mägi, R, Meacham, S, Okada, Y, Pirastu, Nicola, Sorice, R, Teumer, A, Zhang, W, Ramirez Solis, R, Bis, Jc, Ellinghaus, D, Gögele, M, Hottenga, Jj, Langenberg, C, Kovacs, P, F., P, Shin, Sy, Esko, T, Hartiala, J, Kanoni, S, Murgia, F, Parsa, A, Stephens, J, van der Harst, P, van der Schoot, C, Allayee, H, Attwood, A, Balkau, B, Bastardot, F, Basu, S, Baumeister, Se, Biino, G, Bomba, L, Bonnefond, A, Cambien, F, Chambers, Jc, Cucca, F, D'Adamo, ADAMO PIO, Davies, G, de Geus, Ej, de Boer, Ra, Döring, A, Elliott, P, Erdmann, J, Feng, W, Evans, Dm, Falchi, M, Folsom, Ar, Frazer, Ih, Gibson, Qd, Glazer, Nl, Hammond, C, Hartikainen, Al, Heckbert, Sr, Hengstenberg, C, Hersch, M, Illig, T, Loos, Rj, Jolley, J, Khaw, Kt, Kühnel, B, Kyrtsonis, Mc, Lagou, V, Lumley, T, Mangino, M, Maschio, A, Mateo Leach, I, Mcknight, B, Memari, Y, Mitchell, Bd, Montgomery, Gw, Nöthlings, U, Nakamura, Y, Nauck, M, Navis, G, Nolte, Im, Porteous, Dj, Pouta, A, Pramstaller, Pp, Pullat, J, Ring, Sm, Rotter, Ji, Ruggiero, D, Ruokonen, A, Sala, C, Samani, Nj, Sambrook, J, Schlessinger, D, Schreiber, S, Schunkert, H, Scott, J, Smith, Nl, Snieder, H, Starr, Jm, Stumvoll, M, Takahashi, A, Taylor, K, Tenesa, A, Thein, Sl, Tönjes, A, Uda, M, Ulivi, S, Wichmann, He, Yang, Tp, van Veldhuisen, Dj, Visscher, Pm, Völker, U, Wiggins, Kl, Willemsen, G, Zhao, Jh, Zitting, P, Bradley, Jr, Dedoussis, Gv, Gasparini, Paolo, Hazen, Sl, Metspalu, A, Pirastu, M, Shuldiner, Ar, van Pelt, L, Zwaginga, Jj, Boomsma, Di, Deary, Ij, Franke, A, Froguel, P, Ganesh, Sk, Jarvelin, Mr, Martin, Ng, Meisinger, C, Psaty, Bm, Spector, Td, Wareham, Nj, Akkerman, Jw, Ciullo, M, Deloukas, P, Greinacher, A, Jupe, S, Kamatani, N, Khadake, J, Kooner, J, Penninger, J, Prokopenko, I, Stemple, D, Toniolo, D, Wernisch, L, Sanna, S, Hicks, Aa, Ferreira, Ma, Italiano JE, Jr, Gottgens, B, Soranzo, N, Ouwehand, Wh, Biological Psychology, and EMGO+ - Mental Health
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Netherlands Twin Register (NTR) ,Transcription, Genetic ,Gene Expression ,Biochemistry ,megakaryocyte ,Mice ,DNM3 promoter ,Transcription (biology) ,GWAS ,Platelet ,Thrombopoiesis ,Myeloid Ecotropic Viral Integration Site 1 Protein ,Promoter Regions, Genetic ,Cells, Cultured ,Reverse Transcriptase Polymerase Chain Reaction ,Hematology ,Neoplasm Proteins ,Haematopoiesis ,Transcription Initiation Site ,Megakaryocytes ,platelet volume ,DNM3 ,megakaryocytes ,MEIS1 ,Blood Platelets ,Chromatin Immunoprecipitation ,Immunology ,Biology ,Polymorphism, Single Nucleotide ,MEIS1 binding site ,SDG 3 - Good Health and Well-being ,Cell Line, Tumor ,Animals ,Humans ,Cell Lineage ,Binding site ,Gene ,Transcription factor ,Homeodomain Proteins ,Binding Sites ,Genome, Human ,Platelet Count ,Hydrazones ,Genetic Variation ,Cell Biology ,Sequence Analysis, DNA ,Platelets and Thrombopoiesis ,Molecular biology ,Dynamin III - Abstract
We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.
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- 2013
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23. Genetically Determined Height and Coronary Artery Disease
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Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, N, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, U, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, Kooner,JS, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Other departments, Lee Kong Chian School of Medicine (LKCMedicine), Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Burgess, Stephen [0000-0001-5365-8760], Wareham, Nicholas [0000-0003-1422-2993], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
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systolic blood pressure ,Pathology ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,genetic association ,genotype ,cholesterol blood level ,insulin blood level ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,genetic risk ,Triglyceride ,low density lipoprotein cholesterol ,Coronary artery disease ,0302 clinical medicine ,high density lipoprotein cholesterol ,single nucleotide polymorphism ,Risk Factors ,genetic variability ,Odds Ratio ,hyperlipidemia ,Science::Medicine [DRNTU] ,genetics ,glucose ,risk ,0303 health sciences ,medicine.diagnostic_test ,non insulin dependent diabetes mellitus ,Medicine (all) ,allele ,insulin ,triacylglycerol ,triacylglycerol, adult ,aged ,Article ,atherosclerosis ,bioinformatics ,body height ,body mass ,cardiovascular risk ,controlled study ,coronary artery disease ,development ,diastolic blood pressure ,female ,glucose blood level ,human ,major clinical study ,male ,mean arterial pressure ,priority journal ,pulse pressure ,risk factor ,smoking ,triacylglycerol blood level ,blood ,complication ,risk, Adult ,Body Height ,Cholesterol, LDL ,Genetic Variation ,Humans ,Hyperlipidemias ,Triglycerides ,General Medicine ,Cholesterol ,Cardiology ,Adult ,medicine.medical_specialty ,Inverse Association ,Single-nucleotide polymorphism ,Endocrinology and Diabetes ,LDL ,03 medical and health sciences ,Internal medicine ,medicine ,Risk factor ,030304 developmental biology ,Genetic association ,business.industry ,Odds ratio ,medicine.disease ,Lipid profile ,business ,Body mass index - Abstract
BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P
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- 2015
24. Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction
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Lucas G1, Lluís-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP, Sentí M, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Schwartz SM, Siscovick D, O'Donnell CJ, Melander O, Salomaa V, Purcell S, Altshuler D, Samani NJ, Kathiresan S, Elosua R, Voight BF, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, Peltonen L, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Yee J, Friedlander Y, Marrugat J, Lucas G, Sala J, Ramos R, Meigs JB, Williams G, Nathan DM, MacRae CA, Havulinna AS, Berglund G, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Stratton MR, Todd JA, Worthington J, Burton PR, Clayton DG, Cardon LR, Craddock N, Duncanson A, Barrett JC, Davison D, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Ball SG, Balmforth AJ, Barrett JH, Bishop D, Iles MM, Maqbool A, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Cardo LR, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdottir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Lucas, G1, Lluís-Ganella, C, Subirana, I, Musameh, Md, Gonzalez, Jr, Nelson, Cp, Sentí, M, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Schwartz, Sm, Siscovick, D, O'Donnell, Cj, Melander, O, Salomaa, V, Purcell, S, Altshuler, D, Samani, Nj, Kathiresan, S, Elosua, R, Voight, Bf, Musunuru, K, Ardissino, D, Mannucci, Pm, Anand, S, Engert, Jc, Schunkert, H, Erdmann, J, Reilly, Mp, Rader, Dj, Morgan, T, Spertus, Ja, Stoll, M, Girelli, D, Mckeown, Pp, Patterson, Cc, Peltonen, L, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Lucas, G, Sala, J, Ramos, R, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, Havulinna, A, Berglund, G, Deloukas, P, Donnelly, P, Farrall, M, Gough, Sc, Hall, A, Hattersley, At, Hill, Av, Kwiatkowski, Dp, Mathew, Cg, Mccarthy, Mi, Ouwehand, Wh, Parkes, M, Pembrey, M, Rahman, N, Stratton, Mr, Todd, Ja, Worthington, J, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Duncanson, A, Barrett, Jc, Davison, D, Easton, D, Evans, D, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Ball, Sg, Balmforth, Aj, Barrett, Jh, Bishop, D, Iles, Mm, Maqbool, A, Braund, P, Dixon, Rj, Mangino, M, Stevens, S, Thompson, Jr, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Cardo, Lr, Cardin, Nj, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, Ib, Howie, Bn, Su, Z, Teo, Yy, and Vukcevic, D
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Heredity ,Epidemiology ,Myocardial Infarction ,lcsh:Medicine ,Genome-wide association study ,Coronary Artery Disease ,Cardiovascular ,Logistic regression ,Risk Factors ,Cardiac and Cardiovascular Systems ,lcsh:Science ,Genetics ,0303 health sciences ,Multidisciplinary ,Medicine (all) ,030305 genetics & heredity ,Genomics ,Genetic Epidemiology ,Medicine ,Research Article ,Human ,Risk ,Genotype ,Genotypes ,Reproducibility of Result ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genome Analysis Tools ,Genome-Wide Association Studies ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Allele frequency ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Biochemistry, Genetics and Molecular Biology (all) ,Complex Traits ,Risk Factor ,lcsh:R ,Reproducibility of Results ,Human Genetics ,Epistasis, Genetic ,Odds ratio ,Genetic epidemiology ,Agricultural and Biological Sciences (all) ,Genetics of Disease ,Epistasis ,Genetic Polymorphism ,Infart de miocardi -- Epidemiologia ,lcsh:Q ,Population Genetics ,Genome-Wide Association Study - Abstract
The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3–2.0, depending on allele frequency and interaction model).
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- 2012
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25. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
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Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira Gale J, Hallgrimsdóttir IB, Bowie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, CASARI , GIORGIO NEVIO, Reilly, Mp, Li, M, He, J, Ferguson, Jf, Stylianou, Im, Mehta, Nn, Burnett, M, Devaney, Jm, Knouff, Cw, Thompson, Jr, Horne, Bd, Stewart, Af, Assimes, Tl, Wild, P, Allayee, H, Nitschke, Pl, Patel, R, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Martinelli, N, Girelli, D, Quyyumi, Aa, Anderson, Jl, Erdmann, J, Hall, A, Schunkert, H, Quertermous, T, Blankenberg, S, Hazen, Sl, Roberts, R, Kathiresan, S, Samani, Nj, Epstein, Se, Rader, Dj, Qasim, An, Derohannessian, Sl, Qu, L, Cappola, Tp, Chen, Z, Matthai, W, Hakonarson, Hh, Wilensky, R, Kent, Km, Lindsay, Jm, Pichard, Ad, Satler, L, Waksman, R, Knoupf, Cw, Walker, Mc, Waterworth, Dm, Mosser, V, Braund, P, Wright, B, Balmforth, Aj, Ball, Sg, Chen, L, Wells, Ga, Mcpherson, R, Lackner, K, Munzel, Tf, Schillert, A, Schnabel, R, Zeller, T, Ziegler, A, Absher, D, Hlatky, Ma, Iribaren, C, Knowles, Jw, Linsel Nitschke, P, König, Ir, Hengstenberg, C, Nahrstaedt, J, Peters, A, Schreiber, S, Wichmann, E, Willenborg, C, Su, S, Bouzyk, M, Vaccarino, V, Zafari, Am, Carlquist, Jf, Muhlestein, Jb, Olivieri, O, Barnard, J, Hartiala, J, Tang, Wh, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, Dp, Mccarthy, Mi, Ouwehand, Wh, Todd, Ja, Donnelly, P, Barrett, Jc, Davison, D, Easton, D, Evans, Dm, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon Smith, K, Jones, L, Fraser, C, Green, Ek, Grozeva, D, Hamshere, Ml, Holmans, Pa, Jones, Ir, Kirov, G, Moskvina, V, Nikolov, I, O'Donovan, Mc, Owen, Mj, Collier, Da, Elkin, A, Farmer, A, Williamson, R, Mcguffin, P, Young, Ah, Ferrier, In, Barrett, Jh, Bishop, Dt, Iles, Mm, Maqbool, A, Yuldasheva, N, Dixon, Rj, Mangino, M, Stevens, S, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, Cw, Nimmo, Er, Satsangi, J, Fisher, Sa, Forbes, A, Lewis, Cm, Onnie, Cm, Prescott, Nj, Sanderson, J, Mathew, Cg, Barbour, J, Mohiuddin, Mk, Todhunter, Ce, Mansfield, Jc, Ahmad, T, Cummings, Fr, Jewell, Dp, Webster, J, Brown, Mj, Lathrop, M, Connell, J, Dominiczak, A, Marcano, Ca, Burke, B, Dobson, R, Gungadoo, J, Lee, Kl, Munroe, Pb, Newhouse, Sj, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, In, Donovan, H, Eyre, S, Gilbert, Pd, Hider, Sl, Hinks, Am, John, Sl, Potter, C, Silman, Aj, Symmons, Dp, Thomson, W, Worthington, J, Dunger, Db, Widmer, B, Frayling, Tm, Freathy, Rm, Lango, H, Perry, Jr, Shields, Bm, Weedon, Mn, Hattersley, At, Hitman, Ga, Walker, M, Elliott, K, Groves, Cj, Lindgren, Cm, Rayner, Nw, Timpson, Nj, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, Av, Bradbury, La, Farrar, C, Pointon, Jj, Wordsworth, P, Brown, Ma, Franklyn, Ja, Heward, Jm, Simmonds, Mj, Gough, Sc, Seal, S, Stratton, Mr, Rahman, N, Ban, M, Goris, A, Sawcer, Sj, Compston, A, Conway, D, Jallow, M, Rockett, Ka, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, Nj, Ferreira, T, Pereira Gale, J, Hallgrimsdóttir, Ib, Bowie, Bn, Su, Z, Teo, Yy, Vukcevic, D, Bentley, D, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, GIORGIO NEVIO, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, D, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, A, Peltonen, L, Melander, O, Berglund, G, Voight, Bf, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Daly, Mj, Purcell, S, Surti, A, Guiducci, C, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, and Gabriel, Sb
- Subjects
Adult ,Male ,medicine.medical_specialty ,Linkage disequilibrium ,ABO ,ADAMTS7 Protein ,ADAMTS7 ,Genome-wide association study ,Coronary Angiography ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,ABO Blood-Group System ,Coronary artery disease ,Gene Frequency ,ABO blood group system ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Myocardial infarction ,Genetic risk factor ,genetic locus ,Coronary atherosclerosis ,Aged ,business.industry ,coronary atherosclerosis ,General Medicine ,Middle Aged ,medicine.disease ,ADAM Proteins ,myocardial infarction ,Genetic Loci ,Cardiology ,Myocardial infarction complications ,Female ,business ,coronary artery disease ,Genome-Wide Association Study - Abstract
BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
- Published
- 2011
26. Genome-wide association study identifies eight loci associated with blood pressure
- Author
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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, 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, Döring 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, Syvänen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Dörr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Völker 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, Völzke 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, PANICO, SALVATORE, Newton Cheh, C, Johnson, T, Gateva, V, Tobin, Md, Bochud, M, Coin, L, Najjar, S, 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, K, 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, J, 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, Salvatore, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, M, Luben, Rn, Crawford, Gj, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, Ll, Collins, F, Jackson, Au, Mohlke, Kl, Stringham, Hm, Valle, Tt, Willer, Cj, Bergman, Rn, Morken, Ma, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, He, Kathiresan, S, Marrugat, J, O'Donnell, Cj, Schwartz, Sm, Siscovick, D, 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, Syvänen, Ac, Tognoni, G, Lakatta, Eg, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, Sb, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, 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, Völzke, H, Uiterwaal, C, van der Schouw, Yt, Numans, Me, Matullo, G, Navis, G, Berglund, G, Bingham, Sa, Kooner, J, 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, and Munroe, Pb
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- 2009
27. Reproducibility of telomere length assessment: an international collaborative study
- Author
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Cooper, Rachel, Martin-Ruiz, CM, Baird, D, Roger, L, Boukamp, P, Krunic, D, Cawthon, R, Dokter, MM, van, der Harst P, Bekaert, S, de, Meyer T, Roos, G, Svenson, U, Codd, V, Samani, NJ, McGlynn, L, Shiels, PG, Pooley, KA, Dunning, AM, Cooper, R, Wong, A, Kingston, A, and von, Zglinicki T
- Abstract
Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories. Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques. Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63–0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant ( P = 0.06). Gel-based and PCR-based techniques were not different in accuracy. Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.
- Published
- 2014
28. Physiological interaction between ADD1 and WNK1-NEDD4L pathways on sodium related blood pressure regulation
- Author
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MANUNTA , PAOLO, LAVERY G, LANZANI C, BRAUND PS, SIMONINI M, BODYCODE C, ZAGATO L, DELLI CARPINI S, TANTARDINI C, BRIONI E, BIANCHI G, SAMANI NJ, Manunta, Paolo, Lavery, G, Lanzani, C, Braund, P, Simonini, M, Bodycode, C, Zagato, L, DELLI CARPINI, S, Tantardini, C, Brioni, E, Bianchi, G, and Samani, Nj
- Abstract
The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for alpha-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (n344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (n=193), and ambulatory 24-hour BP (n=690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GA+AA) showed a consistent effect on renal Na handling (P=0.009) and acute BP response to a saline infusion (P=0.021), BP lowering after thiazide treatment (P=0.008), and nocturnal systolic BP (P=0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides.
- Published
- 2008
29. Identification of heart rate\u2013associated loci and their effects on cardiac conduction and rhythm disorders
- Author
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den Hoed M, Eijgelsheim M, Esko T, Brundel BJ, Peal DS, Evans DM, Nolte IM, Segrxe8 AV, Holm H, Handsaker RE, Westra HJ, Johnson T, Isaacs A, Yang J, Lundby A, Draisma HH, de Geus EJ, Hottenga JJ, Willemsen G, Boomsma DI, CHARGE-AF Consortium, Ellinor PT, Stricker BH, Metspalu A, Perola M, Beckmann JS, Smith GD, Stefansson K, Wareham NJ, Munroe PB, Sibon OC, Milan DJ, Snieder H, Samani NJ, and Loos RJ
- Published
- 2013
30. CHROMOSOME 9P21 LOCUS AND ANGIOGRAPHIC CORONARY ARTERY DISEASE BURDEN: A COLLABORATIVE META-ANALYSIS
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Chan, K, Patel, RS, Newcombe, P, Nelson, CP, Qasim, A, Epstein, SE, Burnett, S, Vaccarino, VL, Zafari, AM, Shah, SH, Anderson, JL, Carlquist, JF, Hartiala, J, Allayee, H, Hinohara, K, Lee, BS, Erl, A, Ellis, KL, Goel, A, Schaefer, AS, Mokhtari, NE, Goldstein, BA, Hlatky, MA, Go, AS, Shen, GQ, Gong, Y, Pepine, C, Laxton, RC, Wittaker, JC, Tang, WHW, Johnson, JA, Wang, QK, Assimes, TL, Noethlings, U, Farrall, M, Watkins, H, Richards, AM, Cameron, VA, Muendlein, A, Drexel, H, Koch, W, Park, JE, Kimura, A, Shen, WF, Simpson, IA, Hazen, SL, Horne, BD, Hauser, ER, Quyyumi, AA, Reilly, MP, Samani, NJ, and Ye, S
- Published
- 2013
31. Identification of seven loci affecting mean telomere length and their association with disease
- Author
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Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, Hottenga JJ, Fischer K, Esko T, Surakka I, Broer L, Nyholt DR, Mateo Leach I, Salo P, Hxe4gg S, Willemsen G, Perola M, Ouwehand W, Kaprio J, Martin NG, van Duijn CM, Hovatta I, Gieger C, Metspalu A, Boomsma DI, Jarvelin MR, Slagboom PE, Thompson JR, Spector TD, van der Harst P, and Samani NJ
- Published
- 2013
32. Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia
- Author
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Stitziel, No, Fouchier, Sw, Sjouke, B, Peloso, Gm, Moscoso, Am, Auer, Pl, Goel, A, Gigante, B, Barnes, Ta, Melander, O, Orho Melander, M, Duga, S, Sivapalaratnam, S, Nikpay, M, Martinelli, Nicola, Girelli, Domenico, Jackson, Rd, Kooperberg, C, Lange, La, Ardissino, D, Mcpherson, R, Farrall, M, Watkins, H, Reilly, Mp, Rader, Dj, de Faire, U, Schunkert, H, Erdmann, J, Samani, Nj, Charnas, L, Altshuler, D, Gabriel, S, Kastelein, Jj, Defesche, Jc, Nederveen, Aj, Kathiresan, S, Hovingh, Gk, National, Heart, Lung, and Blood Institute GO Exome Sequencing Project
- Subjects
autosomal recessive hypercholesterolemia ,autosomal recessive hypercholesterolemia, exome sequencing, LIPA gene mutation ,LIPA gene mutation ,exome sequencing - Published
- 2013
33. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
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den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, Bj, Peal, Ds, Evans, Dm, Nolte, Im, Segrè, Av, Holm, H, Handsaker, Re, Westra, Hj, Johnson, T, Isaacs, A, Yang, J, Lundby, A, Zhao, Jh, Kim, Yj, Go, Mj, Almgren, P, Bochud, M, Boucher, G, Cornelis, Mc, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, Au, Kutalik, Z, Luan, J, Kemp, Jp, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, Me, Njajou, Ot, O'Reilly, Pf, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, Nj, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, Hh, Feitosa, Mf, Kerr, Kf, Lind, Pa, Mihailov, E, Onland Moret NC, Song, C, Weedon, Mn, Xie, W, Yengo, L, Absher, D, Albert, Cm, Alonso, A, Arking, De, de Bakker PI, Balkau, B, Barlassina, C, Benaglio, P, Bis, Jc, Bouatia Naji, N, Brage, S, Chanock, Sj, Chines, Ps, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, Sb, Fischer, K, Fuchsberger, C, de Geus EJ, Goyette, P, Gudnason, V, Harris, Tb, Hartikainen, Al, Havulinna, As, Heckbert, Sr, Hicks, Aa, Hofman, A, Holewijn, S, Hoogstra Berends, F, Hottenga, Jj, Jensen, Mk, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, Kt, Knowles, Jw, Kooner, As, Kors, Ja, Kumari, M, Milani, L, Laiho, P, Lakatta, Eg, Langenberg, C, Leusink, M, Liu, Y, Luben, Rn, Lunetta, Kl, Lynch, Sn, Markus, Mr, Marques Vidal, P, Mateo Leach, I, Mcardle, Wl, Mccarroll, Sa, Medland, Se, Miller, Ka, Montgomery, Gw, Morrison, Ac, Müller Nurasyid, M, Navarro, P, Nelis, M, O'Connell, Jr, O'Donnell, Cj, Ong, Kk, Newman, Ab, Peters, A, Polasek, O, Pouta, A, Pramstaller, Pp, Psaty, Bm, Rao, Dc, Ring, Sm, Rossin, Ej, Rudan, D, Sanna, S, Scott, Ra, Sehmi, Js, Sharp, S, Shin, Jt, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stewart, C, Stringham, Hm, Tarasov, Kv, Uitterlinden, Ag, Vandenput, L, Hwang, Sj, Whitfield, Jb, Wijmenga, C, Wild, Sh, Willemsen, G, Wilson, Jf, Witteman, Jc, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, Jm, Boomsma, Di, Borecki, Ib, van Duijn CM, Ekelund, U, Forouhi, Ng, Froguel, P, Hingorani, A, Ingelsson, E, Kivimaki, M, Kronmal, Ra, Kuh, D, Lind, L, Martin, Ng, Oostra, Ba, Pedersen, Nl, Quertermous, T, Rotter, Ji, van der Schouw YT, Verschuren, Wm, Walker, M, Albanes, D, Arnar, Do, Assimes, Tl, Bandinelli, S, Boehnke, M, de Boer RA, Bouchard, C, Caulfield, Wl, Chambers, Jc, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst WH, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, Wc, Hu, Fb, Huikuri, Hv, Hunter, Dj, Iribarren, C, Isomaa, B, Jarvelin, Mr, Jula, A, Kähönen, M, Kiemeney, La, van der Klauw MM, Kooner, Js, Kraft, P, Iacoviello, Licia, Lehtimäki, T, Lokki, Ml, Mitchell, Bd, Navis, G, Nieminen, Ms, Ohlsson, C, Poulter, Nr, Qi, L, Raitakari, Ot, Rimm, Eb, Rioux, Jd, Rizzi, F, Rudan, I, Salomaa, V, Sever, Ps, Shields, Dc, Shuldiner, Ar, Sinisalo, J, Stanton, Av, Stolk, Rp, Strachan, Dp, Tardif, Jc, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen DJ, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Ys, Olsen, Jv, Visscher, Pm, Willer, C, Franke, L, Global BPgen Consortium, Cardiogram, Consortium, Erdmann, J, Thompson, Jr, PR GWAS Consortium, Pfeufer, A, QRS GWAS Consortium, Sotoodehnia, N, QT IGC Consortium, Newton Cheh, C, CHARGE AF Consortium, Ellinor, Pt, Stricker, Bh, Metspalu, A, Perola, M, Beckmann, Js, Smith, Gd, Stefansson, K, Wareham, Nj, Munroe, Pb, Sibon, Oc, Milan, Dj, Snieder, H, Samani, Nj, Loos, R. J., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Humane Biologie, Epidemiology, Public Health, Clinical Genetics, Surgery, Medical Informatics, Internal Medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, NCA - Brain imaging technology, ACS - Heart failure & arrhythmias, Physiology, Internal medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Molecular Neuroscience and Ageing Research (MOLAR), and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Netherlands Twin Register (NTR) ,Aetiology, screening and detection [ONCOL 5] ,030204 cardiovascular system & hematology ,Arrhythmias ,DISEASE ,Sudden cardiac death ,PR INTERVAL ,0302 clinical medicine ,Gene Frequency ,Heart Rate ,Arrhythmias, Cardiac/genetics ,0303 health sciences ,COMMON VARIANTS ,Dilated cardiomyopathy ,Atrial fibrillation ,Single Nucleotide ,Heart Rate/genetics ,3. Good health ,DROSOPHILA ,LIBRARY ,Cardiology ,QRS DURATION ,Electrical conduction system of the heart ,Metabolic Networks and Pathways ,rhytm ,conduction ,gene ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,Quantitative Trait Loci ,Cardiac/genetics ,Biology ,Polymorphism, Single Nucleotide ,Article ,Sick sinus syndrome ,Heart Conduction System/physiopathology ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Heart Conduction System ,Internal medicine ,Cardiac conduction ,Heart rate ,Genetics ,medicine ,Animals ,Humans ,GENOME-WIDE ASSOCIATION ,Polymorphism ,Health aging / healthy living Cardiovascular diseases [IGMD 5] ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,030304 developmental biology ,QT INTERVAL ,Arrhythmias, Cardiac ,ta3121 ,medicine.disease ,Endocrinology ,Genetic Loci ,Heart failure ,ATRIAL-FIBRILLATION ,Genome-Wide Association Study - Abstract
Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. © 2013 Nature America, Inc. All rights reserved.
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- 2013
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34. Bayesian refinement of association signals for 14 loci in 3 common diseases
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Maller, JB, McVean, G, Byrnes, J, Vukcevic, D, Palin, K, Su, Z, Howson, JMM, Auton, A, Myers, S, Morris, A, Pirinen, M, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Craddock, N, Hurles, M, Ouwehand, W, Parkes, M, Rahman, N, Duncanson, A, Todd, JA, Kwiatkowski, DP, Samani, NJ, Gough, SCL, McCarthy, MI, Deloukas, P, and Donnelly, P
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endocrine system diseases ,Posterior probability ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Single-nucleotide polymorphism ,Genome-wide association study ,Coronary Artery Disease ,Biology ,FTO gene ,Polymorphism, Single Nucleotide ,Article ,Bayes' theorem ,Genetics ,Humans ,CTLA-4 Antigen ,Genetic Predisposition to Disease ,Genetic association ,Cyclin-Dependent Kinase Inhibitor p15 ,Homeodomain Proteins ,tRNA Methyltransferases ,Genes, p16 ,Proteins ,nutritional and metabolic diseases ,Bayes Theorem ,Cyclin-Dependent Kinase 5 ,Graves Disease ,TRNA Methyltransferases ,Diabetes Mellitus, Type 2 ,Genetic Loci ,TCF7L2 ,Transcription Factor 7-Like 2 Protein ,Genome-Wide Association Study ,Transcription Factors - Abstract
To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.
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- 2012
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35. Erratum: Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height ((The American Journal of Human Genetics (2010) 88 (6-18))
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Lanktree, MB, Guo, Y, Murtaza, M, Glessner, JT, Bailey, SD, Onland-Moret, NC, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, CP, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, JS, Shah, S, Taylor, K, Barnard, J, Peters, BJ, Maloney, CM, Lobmeyer, MT, Stanton, A, Zafarmand, MH, Romaine, SPR, Mehta, A, Van Iperen, EPA, Gong, Y, Price, TS, Smith, EN, Kim, CE, Li, YR, Asselbergs, FW, Atwood, LD, Bailey, KM, Bhatt, D, Bauer, F, Behr, ER, Bhangale, T, Boer, JMA, Boehm, BO, Bradfield, JP, Brown, M, Braund, PS, Burton, PR, Carty, C, Chandrupatla, HR, Chen, W, Connell, J, Dalgeorgou, C, De Boer, A, Drenos, F, Elbers, CC, Fang, JC, Fox, CS, Frackelton, EC, Fuchs, B, Furlong, CE, Gibson, Q, Gieger, C, Goel, A, Grobbee, DE, Hastie, C, Howard, PJ, Huang, G-H, Johnson, WC, Li, Q, Kleber, ME, Klein, BEK, Klein, R, Kooperberg, C, Ky, B, Lacroix, A, Lanken, P, Lathrop, M, Li, M, Marshall, V, Melander, O, Mentch, FD, Meyer, NJ, Monda, KL, Montpetit, A, Murugesan, G, Nakayama, K, Nondahl, D, Onipinla, A, Rafelt, S, Newhouse, SJ, Otieno, FG, Patel, SR, Putt, ME, Rodriguez, S, Safa, RN, Sawyer, DB, Schreiner, PJ, Simpson, C, Sivapalaratnam, S, Srinivasan, SR, Suver, C, Swergold, G, Sweitzer, NK, Thomas, KA, Thorand, B, Timpson, NJ, Tischfield, S, Tobin, M, Tomaszewski, M, Verschuren, WMM, Wallace, C, Winkelmann, B, Zhang, H, Zheng, D, Zhang, L, Zmuda, JM, Clarke, R, Balmforth, AJ, Danesh, J, Day, IN, Schork, NJ, De Bakker, PIW, Delles, C, Duggan, D, Hingorani, AD, Hirschhorn, JN, Hofker, MH, Humphries, SE, Kivimaki, M, Lawlor, DA, Kottke-Marchant, K, Mega, JL, Mitchell, BD, Morrow, DA, Palmen, J, Redline, S, Shields, DC, Shuldiner, AR, Sleiman, PM, Smith, GD, Farrall, M, Jamshidi, Y, Christiani, DC, Casas, JP, Hall, AS, Doevendans, PA, Christie, JD, Berenson, GS, Murray, SS, Illig, T, Dorn, GW, Cappola, TP, Boerwinkle, E, Sever, P, Rader, DJ, Reilly, MP, Caulfield, M, Talmud, PJ, Topol, E, Engert, JC, Wang, K, Dominiczak, A, Hamsten, A, Curtis, SP, Silverstein, RL, Lange, LA, Sabatine, MS, Trip, M, Saleheen, D, Peden, JF, Cruickshanks, KJ, März, W, O'Connell, JR, Klungel, OH, Wijmenga, C, Maitland-Van Der Zee, AH, Schadt, EE, Johnson, JA, Jarvik, GP, Papanicolaou, GJ, Grant, SFA, Munroe, PB, North, KE, Samani, NJ, Koenig, W, Gaunt, TR, Anand, SS, Van Der Schouw, YT, Soranzo, N, Fitzgerald, GA, Reiner, A, Hegele, RA, Hakonarson, H, and Keating, BJ
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- 2012
36. Homocysteine and coronary heart disease: Meta-analysis of MTHFR case-control studies, avoiding publication bias
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Holm, H, Thorsteinsdottir, U, Gretarsdottir, S, Gulcher, Jr, Thorgeirsson, G, Andersen, K, Stefansson, K, Parish, S, Bennett, Da, Clarke, R, Peto, R, Sleight, P, Collins, R, Hopewell, Jc, Watkins, H, Saleheen, D, Danesh, J, Rasheed, A, Zaidi, M, Frossard, P, Shah, N, Samuel, M, Tanaka, T, Ozaki, K, Sato, H, Sakata, Y, Komuro, I, Anand, Ss, Yusuf, S, Engert, Jc, Chambers, J, Kooner, J, Armitage, J, Samani, Nj, Braund, Ps, Nelson, Cp, Hall, As, Balmforth, A, Ball, Sg, Kleber, Me, Hoffmann, Mm, März, Wa, Bugert, P, Winkelmann, B, Böhm, Bo, Ouwehand, Wh, Sivapalaratnam, S, Kastelein, Jj, Trip, Md, Bezzina, Cr, Ouwehand, W, Yamada, Y, Elbers, Cc, Onland Moret NC, Bauer, F, van der Schouw YT, Verschuren, Wm, de Boer JM, Wijmenga, C, Hofker, Mh, de Bakker PI, Peters, Bj, Maitland van der Zee AH, de Boer, A, Klungel, Oh, Grobbee, De, Stewart, Af, Roberts, R, Mcpherson, R, Chen, L, Wells, Ga, Reilly, Mm, Li, M, Qu, I, Rader, Dj, Thorand, B, Illig, T, Peters, A, Koenig, W, Assimes, Tl, Fortmann, S, Iribarren, C, Abbate, R, Marcucci, R, Anderson, Jl, Zebrack, Js, Ardissino, D, Merlini, Fm, Bonomi, Ab, Ashfield Watt PA, Clark, Ze, van Bockxmeer FM, Brownrigg, L, Kooner, Js, Ferrer Antunes, C, Palmeiro, A, Fernandez Arcas, N, Reyes Engel, A, Folsom, Ar, Fowkes, Fg, Lee, Aj, Gaziano, Jm, Gemmati, D, Scapoli, Gl, Genest, J, Rozen, R, Girelli, Domenico, Corrocher, Roberto, Rossi, Gb, Meleady, R, Graham, Im, Gulec, S, Hopkins, Pn, Inbal, A, Selighson, U, Jukema, Jw, Litynsky, P, Kluijtmans, La, Kozich, V, Janosikova, B, Ma, J, Stampfer, Mj, Malinow, Mr, Meisel, C, Stangl, K, Morita, H, Nagai, R, Nakai, K, Nordestgaard, Bg, Zacho, J, Rimm, Eb, Schwartz, Sm, Siscovick, Ds, Silberberg, Js, Szczeklik, A, Domagala, Bt, Tanis, Bc, Rosendaal, Fm, Thogersen, Am, Nilsson, Tk, Todesco, L, Tokgozoglu, Sl, Tsai, My, Hanson, Nq, Verhoeff, Bj, Yamakawa Kobayashi, K, Hamaguchi, H., Medical Research Council (MRC), Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Pulmonology, and Other departments
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Homocysteine ,coronary heart disease ,methylene tetrahydrofolate reductase ,Coronary Disease ,FOLIC-ACID ,030204 cardiovascular system & hematology ,PLACEBO-CONTROLLED TRIAL ,Gastroenterology ,Methylenetetrahydrofolate reductase gene ,Placebo-controlled trial ,Cardiovascular-disease ,Mendelian randomization ,Myocardial-infarction ,Vascular-disease ,Common mutation ,B vitamins ,Folic-acid ,Ethnic-groups ,chemistry.chemical_compound ,MTHFR ,risk factors ,publication bias ,GWA ,genome-wide association ,meta-analysis ,0302 clinical medicine ,Polymorphism (computer science) ,030212 general & internal medicine ,Myocardial infarction ,11 Medical and Health Sciences ,Genetics ,biology ,VASCULAR-DISEASE ,General Medicine ,ETHNIC-GROUPS ,3. Good health ,CARDIOVASCULAR-DISEASE ,Meta-analysis ,MENDELIAN RANDOMIZATION ,Medicine ,MTHFR Studies Collaborative Group ,Life Sciences & Biomedicine ,Research Article ,medicine.medical_specialty ,Genotype ,METHYLENETETRAHYDROFOLATE REDUCTASE GENE ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,03 medical and health sciences ,Medicine, General & Internal ,Folic Acid ,Bias ,Internal medicine ,General & Internal Medicine ,medicine ,Humans ,Methylenetetrahydrofolate Reductase (NADPH2) ,Science & Technology ,Polymorphism, Genetic ,business.industry ,Case-control study ,Odds ratio ,Publication bias ,medicine.disease ,COMMON MUTATION ,chemistry ,MYOCARDIAL-INFARCTION ,Methylenetetrahydrofolate reductase ,biology.protein ,B VITAMINS ,business - Abstract
Robert Clarke and colleagues conduct a meta-analysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease., Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR, Editors' Summary Background Coronary heart disease (CHD) is the leading cause of death among adults in developed countries. With age, fatty deposits (atherosclerotic plaques) coat the walls of the coronary arteries, the blood vessels that supply the heart with oxygen and nutrients. The resultant restriction of the heart's blood supply causes shortness of breath, angina (chest pains that are usually relieved by rest), and sometimes fatal heart attacks. Many established risk factors for CHD, including smoking, physical inactivity, being overweight, and eating a fat-rich diet, can be modified by lifestyle changes. Another possible modifiable risk factor for CHD is a high blood level of the amino acid homocysteine. Methylene tetrahydofolate reductase, which is encoded by the MTHFR gene, uses folate to break down and remove homocysteine so fortification of cereals with folate can reduce population homocysteine blood levels. Pooled results from prospective observational studies that have looked for an association between homocysteine levels and later development of CHD suggest that the reduction in homocysteine levels that can be achieved by folate supplementation is associated with an 11% lower CHD risk. Why Was This Study Done? Prospective observational studies cannot prove that high homocysteine levels cause CHD because of confounding, the potential presence of other unknown shared characteristics that really cause CHD. However, an approach called “Mendelian randomization” can test whether high blood homocysteine causes CHD. A common genetic variant of the MTHFR gene—the C677T polymorphism—reduces MTHFR efficiency so TT homozygotes (individuals in whom both copies of the MTHFR gene have the nucleotide thymine at position 677; the human genome contains two copies of most genes) have 25% higher blood homocysteine levels than CC homozygotes. In meta-analyses (statistical pooling of the results of several studies) of published Mendelian randomized studies, TT homozygotes have a higher CHD risk than CC homozygotes. Because gene variants are inherited randomly, they are not subject to confounding, so this result suggests that high blood homocysteine causes CHD. But what if only Mendelian randomization studies that found an association have been published? Such publication bias would affect this aggregate result. Here, the researchers investigate the association of the MTHFR C677T polymorphism with CHD in unpublished datasets that have analyzed this polymorphism incidentally during other genetic studies. What Did the Researchers Do and Find? The researchers obtained 19 unpublished datasets that contained data on the MTHFR C677T polymorphism in thousands of people with and without CHD. Meta-analysis of these datasets indicates that the excess CHD risk in TT homozygotes compared to CC homozygotes was 2% (much lower than predicted from the prospective observational studies), a nonsignificant difference (that is, it could have occurred by chance). When the probable folate status of the study populations (based on when national folic acid fortification legislation came into effect) was taken into account, there was still no evidence that TT homozygotes had an excess CHD risk. By contrast, in an updated meta-analysis of 86 published studies of the association of the polymorphism with CHD, the excess CHD risk in TT homozygotes compared to CC homozygotes was 15%. Finally, in a meta-analysis of randomized trials on the use of vitamin B supplements for homocysteine reduction, folate supplementation had no significant effect on the 5-year incidence of CHD. What Do These Findings Mean? These analyses of unpublished datasets are consistent with lifelong moderate elevation of homocysteine levels having no significant effect on CHD risk. In other words, these findings indicate that circulating homocysteine levels within the normal range are not causally related to CHD risk. The meta-analysis of the randomized trials of folate supplementation also supports this conclusion. So why is there a discrepancy between these findings and those of meta-analyses of published Mendelian randomization studies? The discrepancy is too large to be dismissed as a chance finding, suggest the researchers, but could be the result of publication bias—some studies might have been prioritized for publication because of the positive nature of their results whereas the unpublished datasets used in this study would not have been affected by any failure to publish null results. Overall, these findings reveal a serious example of publication bias and argue against the use of folate supplements as a means of reducing CHD risk. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001177. The American Heart Association provides information about CHD and tips on keeping the heart healthy; it also provides information on homocysteine, folic acid, and CHD, general information on supplements and heart health, and personal stories about CHD The UK National Health Service Choices website provides information about CHD, including personal stories about CHD Information is available from the British Heart Foundation on heart disease and keeping the heart healthy The US National Heart Lung and Blood Institute also provides information on CHD (in English and Spanish) MedlinePlus provides links to many other sources of information on CHD (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
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- 2012
37. PROSPECTIVE ANALYSIS OF THE ASSOCIATION OF INFECTION WITH CAG A BEARING H. PYLORI STRAINS AND CORONARY ARTERY DISEASE
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Singh, R, Patel, H, McMahon, AD, Packard, C, Rathbone, B, and Samani, NJ
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Heart diseases -- Causes of -- Health aspects ,Coronary heart disease -- Diseases -- Health aspects ,Infection -- Health aspects ,Health - Abstract
There has been much debate and conflicting data on the role of chronic infection with H. pylori on risk of coronary artery disease (CAD). In a previous case-control study, although [...]
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- 2001
38. FLOW CYTOMETRIC ASSESSMENT OF PLATELET REACTIVITY IN NORMAL POPULATION: A DETERMINANT OF INTER-INDIVIDUAL RISK OF CORONARY THROMBOSIS?
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Singh, R, Patel, H, Warner, E, Stribling, J, Desouza, P, Goodall, A, and Samani, NJ
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Heart diseases -- Causes of -- Genetic aspects ,Coronary heart disease -- Genetic aspects ,Flow cytometry -- Genetic aspects -- Physiological aspects ,Glycoproteins -- Physiological aspects -- Genetic aspects ,Fibrinogen -- Physiological aspects -- Genetic aspects ,Blood platelets -- Activation ,Health ,Physiological aspects ,Genetic aspects ,Causes of - Abstract
Background: The key event leading to acute coronary syndromes is the formation of a platelet-rich thrombus at the site of fissuring of an atherosclerotic coronary plaque. Although exposure of a [...]
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- 2001
39. Erratum: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution (Nature Genetics (2010) 42 (949-960))
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Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Vernon Smith, A, Visscher, PM, Yang, J, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, J-J, Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, MJ, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proença, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, M-L, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, J-O, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, SR, Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dörr, M, Elliott, P, Erdos, MR, Eriksson, JG, Freimer, NB, Fu, M, Gaget, S, Geus, EJC, Gjesing, AP, Grallert, H, Gräßler, J, Groves, CJ, Guiducci, C, Hartikainen, A-L, Hassanali, N, Havulinna, AS, Herzig, K-H, Hicks, AA, Hui, J, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, M-L, Luben, RN, Ludwig, B, McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Paré, G, Parker, AN, Peden, JF, Pichler, I, Pietiläinen, KH, Platou, CGP, Pouta, A, Ridderstråle, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, Van Meurs, JBJ, Van Ommen, G-J, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kähönen, M, Lehtimäki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, PM, Stumvoll, M, Tönjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H, Smith, GD, Ebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jørgensen, T, Karpe, F, Khaw, K-T, Laakso, M, Lawlor, DA, Marre, M, Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, JS, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, AT, Hofman, A, Hu, FB, Illig, T, Iribarren, C, Jarvelin, M-R, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, BW, Pramstaller, PP, Psaty, BM, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, TD, Syvanen, A-C, Uda, M, Uitterlinden, A, Völzke, H, Vollenweider, P, Wilson, JF, Witteman, JC, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, H-E, Thorsteinsdottir, U, Van Duijn, CM, Stefansson, K, Cupples, LA, Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL, and Lindgren, CM
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- 2011
40. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
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Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Dörr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, AC, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, JJ, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, X, Lehtimäki, T, Kühnel, B, Lopez, LM, Polašek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FU, Rivadeneira, F, Sijbrands, EJ, Uitterlinden, AG, Hwang, SJ, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Völker, U, Völzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, ML, Aulchenko, Y, Barroso, I, Khaw, KT, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sõber, S, Lu, X, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco, F, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, SY, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJ, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, LifeLines Cohort Study, van der Klauw, MM, Zhang, W, Li, X, Scott, J, Chen, YD, Burke, GL, Kähönen, M, Viikari, J, Döring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, Hoen, PA, König, IR, EchoGen consortium, Felix, JF, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, Destefano, AL, Fornage, M, AortaGen Consortium, Mitchell, GF, CHARGE Consortium Heart Failure Working Group, Smith, NL, KidneyGen consortium, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, CKDGen consortium, Cardiogenics consortium, CardioGram, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, HE, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJ, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JC, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, MR, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P, and van Duijn, CM
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- 2011
41. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data
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Wensley, F, Gao, P, Burgess, S, Kaptoge, S, Di Angelantonio, E, Shah, T, Engert, JC, Clarke, R, Davey-Smith, G, Nordestgaard, BG, Saleheen, D, Samani, NJ, Sandhu, M, Anand, S, Pepys, MB, Smeeth, L, Whittaker, J, Casas, JP, Thompson, SG, Hingorani, AD, Danesh, J, Eiriksdottir, G, Harris, TB, Launer, LJ, Gudnason, V, Folsom, AR, Andrews, G, Ballantyne, CM, Hall, AS, Braund, PS, Balmforth, AJ, Whincup, PH, Morris, R, Lawlor, DA, Lowe, GDO, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Tybjaerg-Hansen, A, Zacho, J, Brown, M, Ricketts, SL, Ashford, S, Lange, L, Reiner, A, Cushman, M, Tracy, R, Wu, C, Ge, J, Zou, Y, Sun, A, Hung, J, McQuillan, B, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Wanner, C, Drechsler, C, Hoffmann, MM, Fowkes, FGR, Tzoulaki, I, Kumari, M, Miller, M, Marmot, M, Onland-Moret, C, van der Schouw, YT, Boer, JM, Wijmenga, C, Khaw, K-T, Vasan, RS, Schnabel, RB, Yamamoto, JF, Benjamin, EJ, Schunkert, H, Erdmann, J, Koenig, IR, Hengstenberg, C, Chiodini, B, Franzosi, MG, Pietri, S, Gori, F, Rudock, M, Liu, Y, Lohman, K, Humphries, SE, Hamsten, A, Norman, PE, Hankey, GJ, Jamrozik, K, Rimm, EB, Pai, JK, Psaty, BM, Heckbert, SR, Bis, JC, Yusuf, S, Xie, C, Collins, R, Bennett, D, Kooner, J, Chambers, J, Elliott, P, Maerz, W, Kleber, ME, Boehm, BO, Winkelmann, BR, Melander, O, Berglund, G, Koenig, W, Thorand, B, Baumert, J, Peters, A, Manson, J, Cooper, JA, Talmud, PJ, Ladenvall, P, Johansson, L, Jansson, J-H, Hallmans, G, Reilly, MP, Qu, L, Li, M, Rader, DJ, Watkins, H, Hopewell, J, Frossard, P, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, Dehghan, A, de Faire, U, Bennet, A, Gigante, B, Leander, K, Peters, B, Maitland-van der Zee, AH, de Boer, A, Klungel, O, Greenland, P, Dai, J, Liu, S, Brunner, E, Kivimaki, M, O'Reilly, D, Ford, I, Packard, CJ, Dis, CRPCH, CIHDS, CC, CUPID, C, Medical Research Council (MRC), University of Groningen, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Pulmonology, and Coronel Institute of Occupational Health
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Male ,Coronary Disease ,Bioinformatics ,Gene Frequency ,MARKERS ,Polymorphism (computer science) ,Risk Factors ,Myocardial infarction ,Prospective Studies ,Prospective cohort study ,General Environmental Science ,Genetics ,RISK ,biology ,General Engineering ,Mendelian Randomization Analysis ,General Medicine ,Middle Aged ,C-Reactive Protein ,1117 Public Health And Health Services ,CARDIOVASCULAR-DISEASE ,Meta-analysis ,symbols ,Female ,Life Sciences & Biomedicine ,Ischaemic Heart Disease ,Polymorphism, Single Nucleotide ,Molecular Genetics ,symbols.namesake ,Medicine, General & Internal ,INFLAMMATION ,Drugs: Cardiovascular System ,General & Internal Medicine ,medicine ,INSTRUMENTAL VARIABLES ,Humans ,C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) ,Allele frequency ,METAANALYSIS ,POLYMORPHISMS ,Science & Technology ,business.industry ,Research ,C-reactive protein ,medicine.disease ,GENE ,MYOCARDIAL-INFARCTION ,ATHEROSCLEROSIS ,Mendelian inheritance ,biology.protein ,General Earth and Planetary Sciences ,business - Abstract
Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P
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- 2011
42. Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways
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Soranzo, N, Sanna, S, Wheeler, E, Gieger, C, Radke, D, Dupuis, J, Bouatia-Naji, N, Langenberg, C, Prokopenko, I, Stolerman, E, Sandhu, MS, Heeney, MM, Devaney, JM, Reilly, MP, Ricketts, SL, Stewart, AF, Voight, BF, Willenborg, C, Wright, B, Altshuler, D, Arking, D, Balkau, B, Barnes, D, Boerwinkle, E, Böhm, B, Bonnefond, A, Bonnycastle, LL, Boomsma, DI, Bornstein, SR, Böttcher, Y, Bumpstead, S, Burnett-Miller, MS, Campbell, H, Cao, A, Chambers, J, Clark, R, Collins, FS, Coresh, J, de Geus, EJ, Dei, M, Deloukas, P, Döring, A, Egan, JM, Elosua, R, Ferrucci, L, Forouhi, N, Fox, CS, Franklin, C, Franzosi, MG, Gallina, S, Goel, A, Graessler, J, Grallert, H, Greinacher, A, Hadley, D, Hall, A, Hamsten, A, Hayward, C, Heath, S, Herder, C, Homuth, G, Hottenga, JJ, Hunter-Merrill, R, Illig, T, Jackson, AU, Jula, A, Kleber, M, Knouff, CW, Kong, A, Kooner, J, Köttgen, A, Kovacs, P, Krohn, K, Kühnel, B, Kuusisto, J, Laakso, M, Lathrop, M, Lecoeur, C, Li, M, Loos, RJ, Luan, J, Lyssenko, V, Mägi, R, Magnusson, PK, Mälarstig, A, Mangino, M, Martínez-Larrad, MT, März, W, McArdle, WL, McPherson, R, Meisinger, C, Meitinger, T, Melander, O, Mohlke, KL, Mooser, VE, Morken, MA, Narisu, N, Nathan, DM, Nauck, M, O'Donnell, C, Oexle, K, Olla, N, Pankow, JS, Payne, F, Peden, JF, Pedersen, NL, Peltonen, L, Perola, M, Polasek, O, Porcu, E, Rader, DJ, Rathmann, W, Ripatti, S, Rocheleau, G, Roden, M, Rudan, I, Salomaa, V, Saxena, R, Schlessinger, D, Schunkert, H, Schwarz, P, Seedorf, U, Selvin, E, Serrano-Ríos, M, Shrader, P, Silveira, A, Siscovick, D, Song, K, Spector, TD, Stefansson, K, Steinthorsdottir, V, Strachan, DP, Strawbridge, R, Stumvoll, M, Surakka, I, Swift, AJ, Tanaka, T, Teumer, A, Thorleifsson, G, Thorsteinsdottir, U, Tönjes, A, Usala, G, Vitart, V, Völzke, H, Wallaschofski, H, Waterworth, DM, Watkins, H, Wichmann, HE, Wild, SH, Willemsen, G, Williams, GH, Wilson, JF, Winkelmann, J, Wright, AF, WTCCC, Zabena, C, Zhao, JH, Epstein, SE, Erdmann, J, Hakonarson, HH, Kathiresan, S, Khaw, KT, Roberts, R, Samani, NJ, Fleming, MD, Sladek, R, Abecasis, G, Boehnke, M, Froguel, P, Groop, L, McCarthy, MI, Kao, WH, Florez, JC, Uda, M, Wareham, NJ, Barroso, I, and Meigs, JB
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endocrine system diseases ,nutritional and metabolic diseases - Published
- 2010
43. Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
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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, Sjögren, 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, Völzke, 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 Consortium, Munroe, P, Caulfield, MJ, Zanchetti, A, and Dominiczak, AF
- Abstract
Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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- 2010
44. Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
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Burgess, Stephen, Thompson, Simon G, CRP CHD Genetics Collaboration, Burgess, S, Thompson, SG, Andrews, G, Samani, NJ, Hall, A, Whincup, P, Morris, R, Lawlor, DA, Davey Smith, G, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Brown, M, Ricketts, S, Sandhu, M, Reiner, A, Psaty, B, Lange, L, Cushman, M, Hung, J, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Nordestgaard, BG, Tybjaerg-Hansen, A, Zacho, J, Wu, C, Lowe, G, Tzoulaki, I, Kumari, M, Yamamoto, JF, Chiodini, B, Franzosi, M, Hankey, GJ, Jamrozik, K, Palmer, L, Rimm, E, Pai, J, Heckbert, S, Bis, J, Anand, S, Engert, J, Collins, R, Clarke, R, Melander, O, Berglund, G, Ladenvall, P, Johansson, L, Jansson, J-H, Hallmans, G, Hingorani, A, Humphries, S, Manson, J, Watkins, H, Hopewell, J, Saleheen, D, Frossard, R, Danesh, J, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, de Faire, U, Bennet, A, Ford, I, Packard, C, Lawlor, Debbie A, Davey Smith, George, Casas, JP, Smeeth, L, Wensley, F, Bowden, J, Di Angelantonio, E, Gao, P, Shah, T, Verzilli, C, Walker, M, Whittaker, J, Danesh, John [0000-0003-1158-6791], Sandhu, Manjinder [0000-0002-2725-142X], Burgess, Stephen [0000-0001-5365-8760], Di Angelantonio, Emanuele [0000-0001-8776-6719], Thompson, Simon [0000-0002-5274-7814], and Apollo - University of Cambridge Repository
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Genetic Markers ,C-Reactive Protein ,Models, Statistical ,Phenotype ,Meta-Analysis as Topic ,Fibrinogen ,Humans ,Bayes Theorem ,Biostatistics ,Polymorphism, Single Nucleotide - Abstract
Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
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- 2010
45. Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
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Burgess, S, Thompson, SG, Andrews, G, Samani, NJ, Hall, A, Whincup, P, Morris, R, Lawlor, DA, Davey Smith, G, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Brown, M, Ricketts, S, Sandhu, M, Reiner, A, Psaty, B, Lange, L, Cushman, M, Hung, J, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Nordestgaard, BG, Tybjaerg-Hansen, A, Zacho, J, Wu, C, Lowe, G, Tzoulaki, I, Kumari, M, Yamamoto, JF, Chiodini, B, Franzosi, M, Hankey, GJ, Jamrozik, K, Palmer, L, Rimm, E, Pai, J, Heckbert, S, Bis, J, Anand, S, Engert, J, Collins, R, Clarke, R, Melander, O, Berglund, G, Ladenvall, P, Johansson, L, Jansson, JH, Hallmans, G, Hingorani, A, Humphries, S, Manson, J, Watkins, H, Hopewell, J, Saleheen, D, Frossard, R, Danesh, J, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JC, Kardys, I, de Faire, U, Bennet, A, Ford, I, Packard, C, Casas, JP, Smeeth, L, Wensley, F, Bowden, J, Di Angelantonio, E, Gao, P, Shah, T, Verzilli, C, Walker, M, and Whittaker, J
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Genetic Markers ,Statistics and Probability ,Epidemiology ,Bayesian probability ,Context (language use) ,Bayes Theorem ,Biostatistics ,Polymorphism, Single Nucleotide ,Article ,Hierarchical database model ,Bayes' theorem ,Meta-Analysis as Topic ,Statistics ,Mendelian randomization ,Econometrics ,Humans ,Models, Statistical ,Instrumental variable ,C-Reactive Protein/genetics/metabolism ,Fibrinogen ,Regression ,Fibrinogen/metabolism ,C-Reactive Protein ,Phenotype ,Meta-analysis - Abstract
Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes. Stat Med
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- 2010
46. Erratum
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Lindgren, CM, Heid, IM, Randall, JC, Lamina, C, Steinthorsdottir, V, Qi, L, Speliotes, EK, Thorleifsson, G, Willer, CJ, Herrera, BM, Jackson, AU, Lim, N, Scheet, P, Soranzo, N, Amin, N, Aulchenko, YS, Chambers, JC, Drong, A, Luan, J, Lyon, HN, Rivadeneira, F, Sanna, S, Timpson, NJ, Zillikens, MC, Zhao, JH, Almgren, P, Bandinelli, S, Bennett, AJ, Bergman, RN, Bonnycastle, LL, Bumpstead, SJ, Chanock, SJ, Cherkas, L, Chines, P, Coin, L, Cooper, C, Crawford, G, Doering, A, Dominiczak, A, Doney, AS, Ebrahim, S, Elliott, P, Erdos, MR, Estrada, K, Ferrucci, L, Fischer, G, Forouhi, NG, Gieger, C, Grallert, H, Groves, CJ, Grundy, S, Guiducci, C, Hadley, D, Hamsten, A, Havulinna, AS, Hofman, A, Holle, R, Holloway, JW, Illig, T, Isomaa, B, Jacobs, LC, Jameson, K, Jousilahti, P, Karpe, F, Kuusisto, J, Laitinen, J, Lathrop, GM, Lawlor, DA, Mangino, M, McArdle, WL, Meitinger, T, Morken, MA, Morris, AP, Munroe, P, Narisu, N, Nordström, A, Nordström, P, Oostra, BA, Palmer, CN, Payne, F, Peden, JF, Prokopenko, I, Renström, F, Ruokonen, A, Salomaa, V, Sandhu, MS, Scott, LJ, Scuteri, A, Silander, K, Song, K, Yuan, X, Stringham, HM, Swift, AJ, Tuomi, T, Uda, M, Vollenweider, P, Waeber, G, Wallace, C, Walters, GB, Weedon, MN, Witteman, JC, Zhang, C, Zhang, W, Caulfield, MJ, Collins, FS, Davey Smith, G, Day, IN, Franks, PW, Hattersley, AT, Hu, FB, Jarvelin, MR, Kong, A, Kooner, JS, Laakso, M, Lakatta, E, Mooser, V, Morris, AD, Peltonen, L, Samani, NJ, Spector, TD, Strachan, DP, Tanaka, T, Tuomilehto, J, Uitterlinden, AG, van Duijn, CM, Wareham, NJ, Watkins For The Procardis Consortia, H, Waterworth, DM, Boehnke, M, Deloukas, P, Groop, L, Hunter, DJ, Thorsteinsdottir, U, Schlessinger, D, Wichmann, HE, Frayling, TM, Abecasis, GR, Hirschhorn, JN, Loos, RJ, Stefansson, K, Mohlke, KL, Barroso, I, and McCarthy For The Giant Consortium, MI
- Abstract
[This corrects the article on p. e1000508 in vol. 5, PMID: 19557161.].
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- 2009
47. Genome-wide association study identifies eight loci associated with blood pressure
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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, Döring, 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, Syvänen, AC, Tognoni, G, Lakatta, EG, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, SB, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, 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, Völzke, 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, and Munroe, PB
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- 2009
48. SVEP1 is a new regulator of arterial tone.
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Morris, GE, Denniff, MJ, Kostogrys, RB, Bountziouka, V, Rainbow, RD, Samani, NJ, and Webb, TR
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VASCULAR smooth muscle ,BLOOD pressure ,HUMAN experimentation ,MESENTERIC artery ,CARDIAC contraction ,SMALL molecules ,BLOOD vessels ,VOLTAGE-gated ion channels - Abstract
Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Introduction Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins can directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Integrin α9β1 has been identified as preventing exaggerated airway bronchiole contraction. Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, are associated with elevated blood pressure, however, neither SVEP1 nor integrin α9β1 have a reported role in vasoregulation. Purpose To determine whether SVEP1 and integrin α9β1 regulate blood vessel contraction. Methods & Results Animal experimentation was performed according to ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and "the Principles of laboratory animal care". Immunocytochemical staining showed both ligand and receptor co-localised within the medial layer of the aorta, and in smooth muscle cells in the mesenteric artery. siRNA inhibition of SVEP1 or integrin α9β1 significantly enhanced real-time [Ca2+]i release in isolated human VSMCs to several Gαq/11-vasoconstrictors and to UTP in VSMCs isolated from Svep1+/- mice (Fig. 1A, n=5, P<0.0001). This enhanced cellular contraction was confirmed in blood vessels by wire myography where aortic rings and mesenteric arteries (Fig. 1B, n=10 P<0.0001) from Svep1+/- mice contracted at significantly higher levels than littermate controls. Similar responses were seen in aortic rings when integrin α9β1 was inhibited using the small molecule inhibitor BOP (n=10 P<0.001). Inhibition of VGCCs using nifidepine, or PKC using bisindolylmaleimide (I) prevented this enhanced contraction, suggesting this effect is mediated via VGCCs in a PKC dependent mechanism. Conclusions Our studies reveal a novel role for SVEP1 and integrin α9β1 in reducing vascular hyper-contractility in response to a range of vasoconstrictor agonists through an L-type voltage gated Ca2+ channel-mediated effect. This regulatory mechanism could suggest a possible explanation for the genetic associations with blood pressure, and provide a new treatment strategy for hypertension. [ABSTRACT FROM AUTHOR]
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- 2022
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49. Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing.
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Koskela J, Kähönen M, Nieminen T, Lehtinen R, Viik J, Nikus K, Niemelä K, Kööbi T, Tobin MD, Samani NJ, Turjanmaa V, Pörsti I, and Lehtimäki T
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- 2012
50. Association between anthropometric obesity measures and coronary artery disease: a cross-sectional survey of 16,657 subjects from 444 Polish cities.
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Kaess BM, Jozwiak J, Mastej M, Lukas W, Grzeszczak W, Windak A, Piwowarska W, Tykarski A, Konduracka E, Rygiel K, Manasar A, Samani NJ, and Tomaszewski M
- Abstract
BACKGROUND: Excessive body weight is known to cluster with cardiovascular (CV) risk factors, but it is not clear which anthropometric obesity measure provides best independent predictive value of coronary artery disease (CAD). METHODS AND RESULTS: We explored associations between CAD and four different obesity measures (body mass index (BMI), waist circumference, waist/height and waist/height(2)) in a cohort of 16 657 subjects (40.4% men; 20.8% CAD patients), recruited by 700 primary care physicians in 444 Polish cities. 42.8% of subjects were classified as overweight, 31.7% as obese and 39.8% had abdominal obesity. In univariate analyses all obesity measures correlated with CAD (p>0.001), but waist/height(2) was the strongest discriminator between CAD patients and controls. Age-adjusted and sex-adjusted analyses confirmed a graded increase in CAD risk across distributions of all four obesity measures-1 standard deviation (SD) increase in BMI, waist, waist/height and waist/height(2) increased the odds of CAD by 1.23, 1.24, 1.26 and 1.27, respectively (all p<0.001). In models fully adjusted for CV risk factors, waist/height(2) remained the strongest obesity correlate of CAD, being the only independent associate of CAD in men. In a fully adjusted BMI-waist circumference stratified model, sarcopenic obesity (waist > median, BMI < median) and simple obesity (waist and BMI > median) were the strongest independent associates of CAD in men (p = 0.008) and women (p>0.001), respectively. CONCLUSION: This cross-sectional study showed that waist/height(2) may potentially offer a slightly higher predictive value of CAD than BMI or waist circumference and revealed an apparent sexual dimorphism in correlations between obesity measures and CAD. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
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