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1. Understanding deprescribing of preventive cardiovascular medication: a Q-methodology study in patients

Author

Luymes CH, Boelhouwer NJ, Poortvliet RKE, de Ruijter W, Reis R, and Numans ME

Subjects
General Practice, Preventive Medicine, Cardiovascular Diseases, Antihypertensive Agents, Anticholesteremic Agents, Inappropriate Prescribing, Medicine (General), R5-920
Abstract

Clare H Luymes,1 Nelleke J Boelhouwer,1 Rosalinde KE Poortvliet,1 Wouter de Ruijter,1 Ria Reis,1–3 Mattijs E Numans1 1Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2Amsterdam Institute for Social Science Research, University of Amsterdam, Amsterdam, the Netherlands; 3The Children’s Institute, University of Cape Town, Cape Town, South Africa Background: Patients with low cardiovascular disease (CVD) risk potentially use preventive cardiovascular medication unnecessarily. Our aim was to identify various viewpoints and beliefs concerning the preventive CVD management of patients with low CVD risk using preventive cardiovascular medication. Furthermore, we investigated whether certain viewpoints were related to a preference for deprescription or the continuation of preventive cardiovascular medication.Methods: In 2015, we purposively sampled patients from the intervention arm of the Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care (ECSTATIC) trial in the Netherlands for this study. Participants made Q-sorts by ranking 43 statements concerning preventive CVD management from “totally disagree” to “totally agree”. These Q-sorts were analyzed using PQMethod 2.35 software. A varimax procedure presented the distinguishing viewpoints that were favored by our participants. We used group discussion quotations to underline our findings. For validation purposes, we asked participants how well each viewpoint fitted them.Results: Of 291 invited patients, 33 participated. Thirty-one Q-sorts were analyzed. The following three viewpoints were found: 1) a controlling viewpoint, in which patients held the belief that monitoring blood pressure and cholesterol levels is important (n=13, of which seven had their medication deprescribed and six continued their medication); 2) an autonomous viewpoint, in which patients showed a dislike of medication (n=8, of which seven had their medication deprescribed and one had it continued); and 3) an afraid viewpoint, in which patients were fearful of developing CVD (n=8, of which two had their medication deprescribed and six had it continued). Seventy-four percent of the participants believed that the viewpoint to which they were assigned was a good fit.Conclusion: Three well-discriminating viewpoints about preventive CVD management were determined. Knowing and recognizing these viewpoints is effective for general practitioners when discussing the deprescribing of preventive cardiovascular medications with patients and may be used to promote implementation of deprescription. Keywords: general practice, preventive medicine, cardiovascular diseases, antihypertensive agents, anticholesteremic agents, inappropriate prescribing

Published
2017

4. NHG-Standaard Maagklachten

Author

Numans, ME, primary, De Wit, NJ, additional, Dirven, JAM, additional, Hurenkamp, GJB, additional, Meijer, QCM, additional, Muris, JWM, additional, Van der Laan, LR, additional, and Van Balen, JAM, additional

Published
2011
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6. Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Author

Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili, Agudo A, Bonet C, Sala N, Muñoz X, Aranda N, Fonseca-Nunes A, Clavel-Chapelon F, Boutron-Ruault MC, Vineis P, Panico S, Palli D, Tumino R, Grioni S, Quirós JR, Molina E, Navarro C, Barricarte A, Chamosa S, Allen NE, Khaw KT, Bueno-de-Mesquita HB, Siersema PD, Numans ME, Trichopoulou A, Lagiou P, Trichopoulos D, Kaaks R, Canzian F, Boeing H, Meidtner K, Johansson M, Sund M, Manjer J, Overvad K, Tjonneland A, Lund E, Weiderpass E, Jenab M, Fedirko V, Offerhaus GJ, Riboli E, González CA, Jakszyn P, Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili, and Agudo A, Bonet C, Sala N, Muñoz X, Aranda N, Fonseca-Nunes A, Clavel-Chapelon F, Boutron-Ruault MC, Vineis P, Panico S, Palli D, Tumino R, Grioni S, Quirós JR, Molina E, Navarro C, Barricarte A, Chamosa S, Allen NE, Khaw KT, Bueno-de-Mesquita HB, Siersema PD, Numans ME, Trichopoulou A, Lagiou P, Trichopoulos D, Kaaks R, Canzian F, Boeing H, Meidtner K, Johansson M, Sund M, Manjer J, Overvad K, Tjonneland A, Lund E, Weiderpass E, Jenab M, Fedirko V, Offerhaus GJ, Riboli E, González CA, Jakszyn P

Abstract

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

Published
2019

8. Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: an individual participant data meta-analysis

Author

Blom, JW, van den Hout, W, den Elzen, WPJ, Drewes, YM, Bleijenberg, N, Fabbricotti, Isabelle, Jansen, APD, Kempen, GIJM, Koopmans, R, Looman, Willemijn, Melis, RJF, Metzelthin, SF, Moll van Charante, EP, Muntinga, ME, Numans, ME, Ruikes, FGH, Spoorenberg, SLW, Stijnen, T, Suijker, JJ, De Wit, NJ, Wynia, K, Wind, AW, Gussekloo, J, Blom, JW, van den Hout, W, den Elzen, WPJ, Drewes, YM, Bleijenberg, N, Fabbricotti, Isabelle, Jansen, APD, Kempen, GIJM, Koopmans, R, Looman, Willemijn, Melis, RJF, Metzelthin, SF, Moll van Charante, EP, Muntinga, ME, Numans, ME, Ruikes, FGH, Spoorenberg, SLW, Stijnen, T, Suijker, JJ, De Wit, NJ, Wynia, K, Wind, AW, and Gussekloo, J

Published
2018

9. Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European prospective investigation into cancer-eurgast cohort

Author

Companioni O, Bonet C, Mu?oz X, Weiderpass E, Tumino R, Palli D, Agnoli C, Vineis P, Boutron Ruault MC, Racine A, Clavel Chapelon F, Travis RC, Khaw KT, Riboli E, Murphy N, Vergnaud AC, Trichopoulou A, Benetou V, Trichopoulos D, Lund E, Johansen D, Lindkvist B, Johansson M, Sund M, Ardanaz E, S?nchez Cantalejo E, Huerta JM, Dorronsoro M, Ram?n Quir?s J, Tjonneland A, Mortensen LM, Overvad K, Chang Claude J, Rizzato C, Boeing H, de Mesquita HB, Siersema P, Peeters PH, Numans ME, Carneiro F, Licaj I, Freisling H, Sala N, Gonz?lez CA, PANICO, SALVATORE, Companioni, O, Bonet, C, Mu?oz, X, Weiderpass, E, Panico, Salvatore, Tumino, R, Palli, D, Agnoli, C, Vineis, P, Boutron Ruault, Mc, Racine, A, Clavel Chapelon, F, Travis, Rc, Khaw, Kt, Riboli, E, Murphy, N, Vergnaud, Ac, Trichopoulou, A, Benetou, V, Trichopoulos, D, Lund, E, Johansen, D, Lindkvist, B, Johansson, M, Sund, M, Ardanaz, E, S?nchez Cantalejo, E, Huerta, Jm, Dorronsoro, M, Ram?n Quir?s, J, Tjonneland, A, Mortensen, Lm, Overvad, K, Chang Claude, J, Rizzato, C, Boeing, H, de Mesquita, Hb, Siersema, P, Peeters, Ph, Numans, Me, Carneiro, F, Licaj, I, Freisling, H, Sala, N, and Gonz?lez, Ca

Subjects
digestive system diseases
Abstract

Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

Published
2014

10. Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension

Author

Tabara, Y, Kohara, K, Kita, Y, Hirawa, N, Katsuya, T, Ohkubo, T, Hiura, Y, Tajima, A, Morisaki, T, Miyata, T, Nakayama, T, Takashima, N, Nakura, J, Kawamoto, R, Takahashi, N, Hata, A, Soma, M, Imai, Y, Kokubo, Y, Okamura, T, Tomoike, H, Iwai, N, Ogihara, T, Inoue, I, Tokunaga, K, Johnson, T, Caulfield, M, Munroe, P, Global Blood Pressure Genetics Consortium, Umemura, S, Ueshima, H, Collaborators: Newton Cheh C, Miki 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, Silvia, 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, 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, Alessandra, Guarrera, Simonetta, Panico, S, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, 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, Zeleneka, 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, Giuseppe, 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, and Munroe, Pb

Subjects
medicine.medical_specialty, hypertension, Genotype, Single-nucleotide polymorphism, ATP2B1, Biology, Lower risk, Polymorphism, Single Nucleotide, Article, Plasma Membrane Calcium-Transporting ATPases, Asian People, Gene Frequency, Polymorphism (computer science), Internal medicine, genetic variation, Millenium Genome Project, Global BPgen, Genetic variation, Odds Ratio, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, Alleles, Genetic association, Genetics, Analysis of Variance, Odds ratio, Blood pressure, Haplotypes, Case-Control Studies, Hypertension, Millennium genome project, Global Bpgen, Regression Analysis, Genome-Wide Association Study
Abstract

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension ( P =5.3×10 −5 ; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P =4.1×10 −11 ). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P =5.9×10 −4 ). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent ( P =1.4×10 −18 ). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1 , rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P =4.6×10 −7 ) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1 , as well as FGF5 , CYP17A1 , and CSK , to be associated with blood pressure levels and risk of hypertension.

Published
2010

11. Dietary total antioxidant capacity and gastriccancer risk in the European prospective investigation into cancer and nutritionstudy

Author

Serafini M, Jakszyn P, Luján L, Agudo A, Bas Bueno de Mesquita H, van Duijnhoven FJ, Jenab M, Navarro C, Palli D, Boeing H, Wallström P, Regnér S, Numans ME, Carneiro F, Boutron Ruault MC, Clavel Chapelon F, Morois S, Grioni S, Tumino R, Sacerdote C, Ramon Quirós J, Molina Montes E, Huerta Castaño JM, Barricarte A, Amiano P, Khaw KT, Wareham N, Allen NE, Key TJ, Jeurnink SM, Peeters PH, Bamia C, Valanou E, Trichopoulou A, Kaaks R, Lukanova A, Bergmann MM, Lindkvist B, Stenling R, Johansson I, Dahm CC, Overvad K, Jensen M, Olsen A, Tjonneland A, Bakken K, Dumeaux V, Lund E, McCormack V, Rinaldi S, Michaud D, Mouw T, Riboli E, González C.A., PANICO, SALVATORE, Serafini, M, Jakszyn, P, Luján, L, Agudo, A, Bas Bueno de Mesquita, H, van Duijnhoven, Fj, Jenab, M, Navarro, C, Palli, D, Boeing, H, Wallström, P, Regnér, S, Numans, Me, Carneiro, F, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Grioni, S, Panico, Salvatore, Tumino, R, Sacerdote, C, Ramon Quirós, J, Molina Montes, E, Huerta Castaño, Jm, Barricarte, A, Amiano, P, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Jeurnink, Sm, Peeters, Ph, Bamia, C, Valanou, E, Trichopoulou, A, Kaaks, R, Lukanova, A, Bergmann, Mm, Lindkvist, B, Stenling, R, Johansson, I, Dahm, Cc, Overvad, K, Jensen, M, Olsen, A, Tjonneland, A, Bakken, K, Dumeaux, V, Lund, E, Mccormack, V, Rinaldi, S, Michaud, D, Mouw, T, Riboli, E, and González, C. A.

Published
2012

14. Aberrant DNA methylation of cancer-associatedgenes in gastric cancer in the European Prospective Investigation into Cancer andNutrition (EPIC-EURGAST)

Author

Balassiano K, Lima S, Jenab M, Overvad K, Tjonneland A, Boutron Ruault MC, Clavel Chapelon F, Canzian F, Kaaks R, Boeing H, Meidtner K, Trichopoulou A, Laglou P, Vineis P, Palli D, Grioni S, Tumino R, Lund E, Bueno de Mesquita HB, Numans ME, Peeters PH, Ramon Quirós J, Sánchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Hallmans G, Stenling R, Ehrnström R, Regner S, Allen NE, Travis RC, Khaw KT, Offerhaus GJ, Sala N, Riboli E, Hainaut P, Scoazec JY, Sylla BS, Gonzalez CA, Herceg Z., PANICO, SALVATORE, Balassiano, K, Lima, S, Jenab, M, Overvad, K, Tjonneland, A, Boutron Ruault, Mc, Clavel Chapelon, F, Canzian, F, Kaaks, R, Boeing, H, Meidtner, K, Trichopoulou, A, Laglou, P, Vineis, P, Panico, Salvatore, Palli, D, Grioni, S, Tumino, R, Lund, E, Bueno de Mesquita, Hb, Numans, Me, Peeters, Ph, Ramon Quirós, J, Sánchez, Mj, Navarro, C, Ardanaz, E, Dorronsoro, M, Hallmans, G, Stenling, R, Ehrnström, R, Regner, S, Allen, Ne, Travis, Rc, Khaw, Kt, Offerhaus, Gj, Sala, N, Riboli, E, Hainaut, P, Scoazec, Jy, Sylla, B, Gonzalez, Ca, and Herceg, Z.

Published
2011

15. Dietary intake of heme iron and risk of gastriccancer in the European prospective investigation into cancer and nutrition(EURGAST- EPIC) study

Author

Jakszyn P, Agudo A, Lujan Barroso L, Bueno de Mesquita HB, Jenab M, Navarro C, Palli D, Boeing H, Manjer J, Numans ME, Igali L, Boutron Ruault MC, Clavel Chapelon F, Morois S, Grioni S, Tumino R, Sacerdote C, Quirós JR, Molina Montes E, Castaño JM, Barricarte A, Amiano P, Khaw KT, Wareham N, Allen NE, Key TJ, Jeurnink SM, Peeters PH, Bamia C, Valanou E, Trichopoulou A, Kaaks R, Lukanova A, Bergmann MM, Lindkvist B, Stenling R, Johansson I, Dahm CC, Overvad K, Olsen A, Tjonneland A, Skeie G, Broderstad AR, Lund E, Michaud DS, Mouw T, Riboli E, González C.A., PANICO, SALVATORE, Jakszyn, P, Agudo, A, Lujan Barroso, L, Bueno de Mesquita, Hb, Jenab, M, Navarro, C, Palli, D, Boeing, H, Manjer, J, Numans, Me, Igali, L, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Grioni, S, Panico, Salvatore, Tumino, R, Sacerdote, C, Quirós, Jr, Molina Montes, E, Castaño, Jm, Barricarte, A, Amiano, P, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Jeurnink, Sm, Peeters, Ph, Bamia, C, Valanou, E, Trichopoulou, A, Kaaks, R, Lukanova, A, Bergmann, Mm, Lindkvist, B, Stenling, R, Johansson, I, Dahm, Cc, Overvad, K, Olsen, A, Tjonneland, A, Skeie, G, Broderstad, Ar, Lund, E, Michaud, D, Mouw, T, Riboli, E, and González, C. A.

Published
2011

16. Four novel loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In vivo

Author

Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Newton Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar S, Zhao JH, Heath SC, Eyheramendy S, Wallace C, Chambers JC, Khaw KT, Polidoro S, Grobbee DE, Onland Moret NC, Allione A, Di Gregorio A, Guarrera S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder P, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Galan P, Gut IV, Hercberg S, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bandinelli S, Ferrucci L, Watkins H, Tuomilehto J, Altshuler D, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RFJ, Elliott P, Abecasis GR, Caulfield M, Munroe PB, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY, PANICO, SALVATORE, Ophthalmology, Epidemiology, Internal Medicine, Faculteit der Geneeskunde, Ikram, Mk, Xueling, S, Jensen, Ra, Cotch, Mf, Hewitt, Aw, Ikram, Ma, Wang, Jj, Klein, R, Klein, Be, Breteler, Mm, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, Ag, Rivadeneira, F, Hofman, A, de Jong, Pt, van Duijn, Cm, Kao, L, Cheng, Cy, Smith, Av, Glazer, Nl, Lumley, T, Mcknight, B, Psaty, Bm, Jonasson, F, Eiriksdottir, G, Aspelund, T, Panico, Salvatore, Global BPgen, Consortium, Harris, Tb, Launer, Lj, Taylor, Kd, Li, X, Iyengar, Sk, Xi, Q, Sivakumaran, Ta, Mackey, Da, Macgregor, S, Martin, Ng, Young, Tl, Bis, Jc, Wiggins, Kl, Heckbert, Sr, Hammond, Cj, Andrew, T, Fahy, S, Attia, J, Holliday, Eg, Scott, Rj, Islam, Fm, Rotter, Ji, Mcauley, Ak, Boerwinkle, E, Tai, E, Gudnason, V, Siscovick, D, Vingerling, Jr, 2010 Oct 28, Wong T. Y. PLoS G. e. n. e. t., 6:e1001184, Sim, X, Newton Cheh, C, Johnson, T, Gateva, V, Tobin, Md, Bochud, M, Coin, L, Najjar, S, Zhao, Jh, Heath, Sc, Eyheramendy, S, Wallace, C, Chambers, Jc, Khaw, Kt, Polidoro, S, Grobbee, De, Onland Moret, Nc, Allione, A, Di Gregorio, A, Guarrera, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, O'Reilly, Pf, Peltonen, L, Pouta, A, de Jong, Pe, Snieder, P, Tognoni, G, Lakatta, Eg, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Galan, P, Gut, Iv, Hercberg, S, van der Schouw, Yt, Numans, Me, Matullo, G, Navis, G, Berglund, G, Bandinelli, S, Ferrucci, L, Watkins, H, Tuomilehto, J, Altshuler, D, Wareham, Nj, Uda, M, Jarvelin, Mr, Mooser, V, Melander, O, Loos, Rfj, Elliott, P, Abecasis, Gr, Caulfield, M, Munroe, Pb, Wong, Ty, Medical Research Council (MRC), and Department of Public Health

Subjects
Male, Cancer Research, Pathology, VESSEL DIAMETERS, Genome-wide association study, 030204 cardiovascular system & hematology, QH426-470, DISEASE, Pathogenesis, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disorders/Vascular Biology, Child, Genetics (clinical), Genetics, Aged, 80 and over, 0303 health sciences, education.field_of_study, Middle Aged, 314 Health sciences, 3. Good health, Cardiovascular Diseases, Child, Preschool, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Female, Research Article, Adult, medicine.medical_specialty, Adolescent, ANTIHYPERTENSIVE DRUG THERAPIES, Population, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, ATHEROSCLEROSIS RISK, Biology, Polymorphism, Single Nucleotide, White People, Microcirculation, 03 medical and health sciences, Young Adult, AGE, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, Genetics and Genomics/Population Genetics, medicine, SNP, Humans, GENOME-WIDE ASSOCIATION, education, Molecular Biology, Ecology, Evolution, Behavior and Systematics, METAANALYSIS, Global BPgen Consortium, 030304 developmental biology, Aged, 0604 Genetics, Chromosomes, Human, Pair 12, Retinal Vessels, Retinal, CHARGE CONSORTIUM, RETINAL VASCULAR CALIBER, chemistry, Genetic Loci, Ophthalmology/Retinal Disorders, genome-wide association study, microcirculation, GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK, Chromosomes, Human, Pair 19, Developmental Biology, Genome-Wide Association Study
Abstract

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p, Author Summary The microcirculation plays an important role in the development of cardiovascular diseases. Retinal vascular caliber changes reflect early microvascular disease and predict incident cardiovascular events. In order to identify genetic variants associated with retinal vascular caliber, we performed a genome-wide association study and analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). We found evidence for association of four loci with retinal venular caliber: on chromosomes 19q13 within the RASIP1 locus, 6q24 adjacent to the VTA1 and NMBR loci, 12q24 in the region of ATXN2,SH2B3 and PTPN11 loci, and 5q14 adjacent to the MEF2C locus. In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. In the present study, we demonstrate that four novel loci were associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. Our findings will help focus research on novel genes and pathways involving the microcirculation and its role in the development of cardiovascular disease.

Published
2010

17. Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium GenomeProject

Author

Tabara Y, Kohara K, Kita Y, Hirawa N, Katsuya T, Ohkubo T, Hiura Y, Tajima A, Morisaki T, Miyata T, Nakayama T, Takashima N, Nakura J, Kawamoto R, Takahashi N, Hata A, Soma M, Imai Y, Kokubo Y, Okamura T, Tomoike H, Iwai N, Ogihara T, Inoue I, Tokunaga K, Johnson T, Caulfield M, Munroe P, Newton Cheh C, Gateva V, Tobin MD, Bochud M, Coin L, Najjar S, Zhao JH, Heath SC, Eyheramendy S, Wallace C, Chambers JC, Khaw KT, Polidoro S, Grobbee DE, Onland Moret NC, Allione A, Di Gregorio A, Guarrera S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder P, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Galan P, Gut IV, Hercberg S, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bandinelli S, Ferrucci L, Watkins H, Tuomilehto J, Altshuler D, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RFJ, Elliott P, Abecasis GR, Munroe PB, Umemura S, Ueshima H, Miki T., PANICO, SALVATORE, Tabara, Y, Kohara, K, Kita, Y, Hirawa, N, Katsuya, T, Ohkubo, T, Hiura, Y, Tajima, A, Morisaki, T, Miyata, T, Nakayama, T, Takashima, N, Nakura, J, Kawamoto, R, Takahashi, N, Hata, A, Soma, M, Imai, Y, Kokubo, Y, Okamura, T, Tomoike, H, Iwai, N, Ogihara, T, Inoue, I, Tokunaga, K, Johnson, T, Caulfield, M, Munroe, P, Newton Cheh, C, Gateva, V, Tobin, Md, Bochud, M, Coin, L, Najjar, S, Zhao, Jh, Heath, Sc, Eyheramendy, S, Wallace, C, Chambers, Jc, Khaw, Kt, Polidoro, S, Grobbee, De, Onland Moret, Nc, Allione, A, Di Gregorio, A, Guarrera, S, Panico, Salvatore, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, O'Reilly, Pf, Peltonen, L, Pouta, A, de Jong, Pe, Snieder, P, Tognoni, G, Lakatta, Eg, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Galan, P, Gut, Iv, Hercberg, S, van der Schouw, Yt, Numans, Me, Matullo, G, Navis, G, Berglund, G, Bandinelli, S, Ferrucci, L, Watkins, H, Tuomilehto, J, Altshuler, D, Wareham, Nj, Uda, M, Jarvelin, Mr, Mooser, V, Melander, O, Loos, Rfj, Elliott, P, Abecasis, Gr, Munroe, Pb, Umemura, S, Ueshima, H, and Miki, T.

Published
2010

18. Genome-wide association study identifies eight loci associated with blood pressure

Author

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

Published
2009

19. Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study

Author

PERA G, AGUDO A, BUENO DE MESQUITA HB, PALLI D, BOEING H, CARNEIRO F, BERRINO F, SACERDOTE C, TUMINO R, BERGLUND G, MANJER J, JOHANSSON I, STENLING R, MARTINEZ C, DORRONSORO M, BARRICARTE A, TORMO MJ, QUIROS JR, ALLEN N, KEY TJ, BINGHAM S, LINSEISEN J, KAAKS R, OVERVAD K, JENSEN M, OLSEN A, TJONNELAND A, PEETERS PH, NUMANS ME, OCKE MC, CLAVEL CHAPELON F, BOUTRON RUAULT MC, TRICHOPOULOU A, LUND E, SLIMANI N, JENAB M, FERRARI P, RIBOLI E, GONZALEZ CA, PANICO, SALVATORE, Pera, G, Agudo, A, BUENO DE MESQUITA, Hb, Palli, D, Boeing, H, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, Salvatore, Berglund, G, Manjer, J, Johansson, I, Stenling, R, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Allen, N, Key, Tj, Bingham, S, Linseisen, J, Kaaks, R, Overvad, K, Jensen, M, Olsen, A, Tjonneland, A, Peeters, Ph, Numans, Me, Ocke, Mc, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Trichopoulou, A, Lund, E, Slimani, N, Jenab, M, Ferrari, P, Riboli, E, and Gonzalez, Ca

Published
2007

20. Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition

Author

AGUDO A, SALA N, PERA G, CAPELLA G, BERENGUER A, GARCIA N, PALLI D, BOEING, H, DEL GIUDICE G, SAIEVA C, CARNEIRO F, BERRINO F, SACERDOTE C, TUMINO R, S, BERGLUND G, SIMAN H, STENLING R, HALLMANS G, MARTINEZ C, BILBAO R, BARRICARTE, A, NAVARRO C, QUIROS JR, ALLEN N, KEY T, BINGHAM S, KHAW KT, LINSEISEN J, NAGEL, G, OVERVAD K, TJONNELAND A, OLSEN A, BUENO DE MESQUITA HB, BOSHUIZEN HC, PEETERS, PH, NUMANS ME, CLAVEL CHAPELON F, BOUTRON RUAULT MC, TRICHOPOULOU A, LUND E, OFFERHAUS J, JENAB M, FERRARI P, NORAT T, RIBOLI E, GONZALEZ CA, PANICO, SALVATORE, Agudo, A, Sala, N, Pera, G, Capella, G, Berenguer, A, Garcia, N, Palli, D, Boeing, H, DEL GIUDICE, G, Saieva, C, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, Salvatore, S, Berglund, G, Siman, H, Stenling, R, Hallmans, G, Martinez, C, Bilbao, R, Barricarte, A, Navarro, C, Quiros, Jr, Allen, N, Key, T, Bingham, S, Khaw, Kt, Linseisen, J, Nagel, G, Overvad, K, Tjonneland, A, Olsen, A, BUENO DE MESQUITA, Hb, Boshuizen, Hc, Peeters, Ph, Numans, Me, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Trichopoulou, A, Lund, E, Offerhaus, J, Jenab, M, Ferrari, P, Norat, T, Riboli, E, and Gonzalez, Ca

Published
2006

21. No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition

Author

AGUDO A, SALA N, PERA G, CAPELLA G, BERENGUER A, GARCIA N, PALLI D, BOEING, H, DEL GIUDICE G, SAIEVA C, CARNEIRO F, BERRINO F, SACERDOTE C, TUMINO R, S, BERGLUND G, SIMAN H, STENLING R, HALLMANS G, MARTINEZ C, AMIANO P, BARRICARTE, A, NAVARRO C, QUIROS JR, ALLEN N, KEY T, BINGHAM S, KHAW KT, LINSEISEN J, NAGEL, G, OVERVAD K, TJONNELAND A, OLSEN A, BUENO DE MESQUITA HB, BOSHUIZEN HC, PEETERS, PH, NUMANS ME, CLAVEL CHAPELON F, BOUTRON RUAULT MC, TRICHOPOULOU A, LUND E, BLAKER H, JENAB M, FERRARI P, NORAT T, RIBOLI E, GONZALEZ CA, PANICO, SALVATORE, Agudo, A, Sala, N, Pera, G, Capella, G, Berenguer, A, Garcia, N, Palli, D, Boeing, H, DEL GIUDICE, G, Saieva, C, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, Salvatore, S, Berglund, G, Siman, H, Stenling, R, Hallmans, G, Martinez, C, Amiano, P, Barricarte, A, Navarro, C, Quiros, Jr, Allen, N, Key, T, Bingham, S, Khaw, Kt, Linseisen, J, Nagel, G, Overvad, K, Tjonneland, A, Olsen, A, BUENO DE MESQUITA, Hb, Boshuizen, Hc, Peeters, Ph, Numans, Me, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Trichopoulou, A, Lund, E, Blaker, H, Jenab, M, Ferrari, P, Norat, T, Riboli, E, and Gonzalez, Ca

Published
2006

22. Early life lung function and respiratory outcome in the first year of life

Author

van der Ent Ck, de Jong Bm, Numans Me, van Putte-Katier N, Uiterwaal Cs, van der Gugten Ac, Th.J.M. Verheij, and Kimpen Jl

Subjects
Pulmonary and Respiratory Medicine, Male, Pediatrics, medicine.medical_specialty, First year of life, Pulmonary compliance, Risk Factors, Wheeze, Surveys and Questionnaires, medicine, Humans, Respiratory system, Lung, Lung function, Respiratory Sounds, business.industry, Infant, Newborn, Infant, Anthropometry, Early life, respiratory tract diseases, Respiratory Function Tests, Increased risk, Cough, Female, medicine.symptom, business, Follow-Up Studies
Abstract

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires. 836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance ( R rs ) and time constant ( τ rs ) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance ( C rs ) were associated with a decreased risk for wheeze and cough. R rs , C rs and τ rs measured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.

Published
2012

24. Frailty screening in older patients in primary care using routine care data

Author

Brain, Child Health, JC Overig onderzoek, Other research (not in main researchprogram), Cancer, General Practice & Nursing Science, de Wit, Niek, Numans, ME, Schuurmans, M.J., Drubbel, I., Brain, Child Health, JC Overig onderzoek, Other research (not in main researchprogram), Cancer, General Practice & Nursing Science, de Wit, Niek, Numans, ME, Schuurmans, M.J., and Drubbel, I.

Published
2014

25. Genome-wide association study identifies eight loci associated with blood pressure

Author

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

Published
2009

26. No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition

Author

Agudo, A Sala, N Pera, G Capella, G Berenguer, A and Garcia, N Palli, D Boeing, H Del Giudice, G Saieva, C and Carneiro, F Berrino, F Sacerdote, C Tumino, R and Panico, S Berglund, G Siman, H Stenling, R Hallmans, G and Martinez, C Amiano, P Barricarte, A Navarro, C and Quiros, JR Allen, N Key, T Bingham, S Khaw, KT and Linseisen, J Nagel, G Overvad, K Tjonneland, A Olsen, A and Bueno-De-Mesquita, HB Boshuizen, HC Peeters, PH Numans, ME Clavel-Chapelon, F Boutron-Ruault, MC Trichopoulou, A and Lund, E Blaker, H Jenab, M Ferrari, P Norat, T and Riboli, E Gonzalez, CA

Published
2006

27. Peptisch ulcuslijden

Author

Scholten, P (Peter), Kuipers, Ernst, Mathus-Vliegen, EMH, Muris, JWM, Numans, ME, Starmans, R, and Gastroenterology & Hepatology

Published
2005

28. Acute buik bij volwassenen

Author

van de Poll, M.C.G., Dejong, C.H.C., Soeters, P.B., Mathus-Vliegen, EMH, Muris, JWM, Numans, ME, Starmans, R, Algemene Heelkunde, and RS: NUTRIM School of Nutrition and Translational Research in Metabolism

Published
2003

29. A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome

Author

Lewin-van den Broek, NT, Numans, ME, Buskens, E, Verheij, TJM, Smout, AJPM, and Methods in Medicines evaluation & Outcomes research (M2O)

Subjects
GASTROESOPHAGEAL REFLUX DISEASE, therapy, disease management, PREDICTING ENDOSCOPIC DIAGNOSIS, ERADICATION, PRIMARY-CARE, dyspepsia, FUNCTIONAL DYSPEPSIA, randomised controlled trial, PATIENT, HELICOBACTER-PYLORI INFECTION, ULCER
Abstract

Background: The first step in the management of uncomplicated dyspepsia in primary care often consists of prescribing empirical therapy, bite in certain cases prompt endoscopy might be preferred. Any decision is usually based on the patient's symptoms and the presumed underlying pathology that causes these symptoms. Aim: To assess the relationship between symptom subgroups and the effect of management strategies on primary care patients with dyspepsia. Design of study: Randomised controlled trial. Setting. All patients presenting successively with a new episode of dyspepsia between January 1995 and November 1997. Method. The results of four management strategies in dyspeptic primary care patients were compared and the value of subgrouping within this trial was estimated. Patients were allocated to one of either (a) empirical treatment in which therapy was based on the presented symptoms, or empirical treatment with (b) omeprazole or (c) cisapride regardless of the presented symptoms, or (d) prompt endoscopy followed by the appropriate treatment. Patients were retrospectively classified into the subgroups for each strategy using baseline data. The yield of each strategy was measured by counting the number of strategy failures in the first year. Results: Of the 349 included patients, 326 were analysed No statistically significant difference could be demonstrated between the strategies or between the symptom subgroups. However, patients in the reflux-like subgroup showed a trend towards a better outcome in all empirical strategies. Ulcer-like dyspepsia seemed to benefit from omeprazole. The non-specific subgroup seemed to benefit from cisapride but also had the highest proportion of strategy failure. Prompt endoscopy did not appear especially useful in any subgroup. Conclusion: Although this study has relatively low power we conclude that the use of symptom subgroups seems to he a sensible approach when choosing empirical therapy in dyspepsia. Patients with reflux-like symptoms seem to have the best prognosis in the first year in every strategy.

Published
2001

31. Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective investigation into cancer and nutrition

Author

Jeurnink, SM, Büchner, FL, Bueno-de-Mesquita, HB, Siersema, PD, Boshuizen, HC, Numans, ME, Dahm, CC, Overvad, K, Tjønneland, A, Roswall, N, Clavel-Chapelon, F, Boutron-Ruault, MC, Morois, S, Kaaks, R, Teucher, B, Boeing, H, Buijsse, B, Trichopoulou, A, Benetou, V, Zylis, D, Palli, D, Sieri, S, Vineis, P, Tumino, R, Panico, S, Ocké, MC, Peeters, PHM, Skeie, G, Brustad, M, Lund, E, Sánchez-Cantalejo, E, Navarro, C, Amiano, P, Ardanaz, E, Quirós, J Ramón, Hallmans, Göran, Johansson, I, Lindkvist, B, Regnér, S, Khaw, KT, Wareham, N, Key, TJ, Slimani, N, Norat, T, Vergnaud, AC, Romaguera, D, Gonzalez, CA, Jeurnink, SM, Büchner, FL, Bueno-de-Mesquita, HB, Siersema, PD, Boshuizen, HC, Numans, ME, Dahm, CC, Overvad, K, Tjønneland, A, Roswall, N, Clavel-Chapelon, F, Boutron-Ruault, MC, Morois, S, Kaaks, R, Teucher, B, Boeing, H, Buijsse, B, Trichopoulou, A, Benetou, V, Zylis, D, Palli, D, Sieri, S, Vineis, P, Tumino, R, Panico, S, Ocké, MC, Peeters, PHM, Skeie, G, Brustad, M, Lund, E, Sánchez-Cantalejo, E, Navarro, C, Amiano, P, Ardanaz, E, Quirós, J Ramón, Hallmans, Göran, Johansson, I, Lindkvist, B, Regnér, S, Khaw, KT, Wareham, N, Key, TJ, Slimani, N, Norat, T, Vergnaud, AC, Romaguera, D, and Gonzalez, CA

Abstract

BACKGROUND: Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Data on food consumption and follow-up on cancer incidence was available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 non-cardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores (DDSs) were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. RESULTS: Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous HR per 2 products increment 0.88; 95%CI 0.79-0.97 and 0.76; 95%CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. CONCLUSION: Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors can not be excluded. © 2012 Wiley-Liss, Inc.

Published
2012
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32. Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition

Author

Duell, Eric J, Travier, Noémie, Lujan-Barroso, Leila, Boutron-Ruault, MC, Clavel-Chapelon, F, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Rodriguez, Laudina, Sanchez-Cantalejo, Emilio, Navarro, Carmen, Barricarte, Aurelio, Dorronsoro, Miren, Khaw, Kay-Tee, Wareham, Nicholas, Allen, Naomi E, Tsilidis, Konstantinos K, Bueno-de-Mesquita, H Bas, Jeurnink, Suzanne M, Numans, ME, Peeters, Petra HM, Lagiou, Pagona, Valanou, Elisabeth, Trichopoulou, Antonia, Kaaks, Rudolf, Lukanova-McGregor, Annekatrin, Bergman, Manuela M, Boeing, Heiner, Manjer, Jonas, Lindkvist, Björn, Stenling, Roger, Hallmans, Göran, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Bakken, Kjersti, Lund, Eiliv, Jenab, Mazda, McCormack, Valerie, Rinaldi, Sabina, Michaud, Dominique, Mouw, Traci, Nesi, Gabriella, Carneiro, Fatima, Riboli, Elio, González, Carlos A, Duell, Eric J, Travier, Noémie, Lujan-Barroso, Leila, Boutron-Ruault, MC, Clavel-Chapelon, F, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Rodriguez, Laudina, Sanchez-Cantalejo, Emilio, Navarro, Carmen, Barricarte, Aurelio, Dorronsoro, Miren, Khaw, Kay-Tee, Wareham, Nicholas, Allen, Naomi E, Tsilidis, Konstantinos K, Bueno-de-Mesquita, H Bas, Jeurnink, Suzanne M, Numans, ME, Peeters, Petra HM, Lagiou, Pagona, Valanou, Elisabeth, Trichopoulou, Antonia, Kaaks, Rudolf, Lukanova-McGregor, Annekatrin, Bergman, Manuela M, Boeing, Heiner, Manjer, Jonas, Lindkvist, Björn, Stenling, Roger, Hallmans, Göran, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Bakken, Kjersti, Lund, Eiliv, Jenab, Mazda, McCormack, Valerie, Rinaldi, Sabina, Michaud, Dominique, Mouw, Traci, Nesi, Gabriella, Carneiro, Fatima, Riboli, Elio, and González, Carlos A

Abstract

The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.

Published
2010
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36. Studies on gastroesophageal reflux disease

Author

JC Overig onderzoek, Other research (not in main researchprogram), MS MDL 1, Smout, A.J.P.M., Bredenoord, A.J., Numans, ME, Aanen, M.C., JC Overig onderzoek, Other research (not in main researchprogram), MS MDL 1, Smout, A.J.P.M., Bredenoord, A.J., Numans, ME, and Aanen, M.C.

Published
2008

38. Obesity Matters : Findings in the Utrecht Health Project and the Framingham Heart Study

Author

Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epidemiology & Health Economics, Grobbee, Rick, Numans, ME, van Ameijden, E.J.C., Molenaar, E.A., Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epidemiology & Health Economics, Grobbee, Rick, Numans, ME, van Ameijden, E.J.C., and Molenaar, E.A.

Published
2008

39. Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study.

Author

Mendez, M A, Pera, G, Agudo, A, Bueno-de-Mesquita, HB, Palli, D, Boeing, H, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, S, Berglund, G, Manjer, J, Johansson, Ingegerd, Stenling, R, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, MJ, Quiros, JR, Allen, N, Key, TJ, Bingham, S, Linseisen, J, Kaaks, R, Overvad, K, Jensen, M, Olsen, A, Tjonneland, A, Peeters, PH, Numans, ME, Ocké, MC, Clavel-Chapelon, F, Boutron-Ruault, MC, Trichopoulou, A, Lund, E, Slimani, N, Jenab, M, Ferrari, P, Riboli, E, González, CA, Mendez, M A, Pera, G, Agudo, A, Bueno-de-Mesquita, HB, Palli, D, Boeing, H, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, S, Berglund, G, Manjer, J, Johansson, Ingegerd, Stenling, R, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, MJ, Quiros, JR, Allen, N, Key, TJ, Bingham, S, Linseisen, J, Kaaks, R, Overvad, K, Jensen, M, Olsen, A, Tjonneland, A, Peeters, PH, Numans, ME, Ocké, MC, Clavel-Chapelon, F, Boutron-Ruault, MC, Trichopoulou, A, Lund, E, Slimani, N, Jenab, M, Ferrari, P, Riboli, E, and González, CA

Abstract

Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date, different food sources of fiber have not been examined with respect to noncardia tumors or diverse histologic sub-types. This study prospectively examines associations between fiber from different food sources and incident gastric adenocarcinomas (GC) among more than 435,000 subjects from 10 countries participating in the European Prospective Investigation into Cancer and Nutrition study. Subjects aged 25-70 years completed dietary questionnaires in 1992-98, and were followed up for a median of 6.7 years. About 312 incident GCs were observed. The relative risk of GC was estimated based on cohort-wide sex-specific fiber intake quartiles using proportional hazards models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Intakes of cereal fiber, but not total, fruit or vegetable fiber, were associated with reduced GC risk [adjusted HR for the highest vs. lowest quartile of cereal fiber 0.69, 0.48-0.99]. There was a strong inverse association for diffuse [HR 0.43, 0.22-0.86], but not intestinal type [HR 0.98, 0.54-1.80] tumors. Associations for cardia vs. noncardia tumors were similar to those for overall GC, although cardia associations did not reach significance. Cereal fiber consumption may help to reduce risk of GC, particularly diffuse type tumors. Further study on different food sources of fiber in relation to GC risk is warranted to confirm these relationships.

Published
2007
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40. Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Author

Jenab, M, Riboli, E, Ferrari, P, Friesen, M, Sabate, J, Norat, T, Slimani, N, Tjonneland, A, Olsen, A, Overvad, K, Boutron-Ruault, MC, Clavel-Chapelon, F, Boeing, H, Schulz, M, Linseisen, J, Nagel, G, Trichopoulou, A, Naska, A, Oikonomou, E, Berrino, F, Panico, S, Palli, D, Sacerdote, C, Tumino, R, Peeters, PH, Numans, ME, Bueno-de Mesquita, HB, Buchner, FL, Lund, E, Pera, G, Chirlaque, MD, Sanchez, MJ, Arriola, L, Barricarte, A, Quiros, JR, Johansson, Ingegerd, Johansson, Anders, Berglund, G, Bingham, S, Khaw, KT, Allen, N, Key, T, Carneiro, F, Save, V, Del Giudice, G, Plebani, M, Kaaks, R, Gonzalez, CA, Jenab, M, Riboli, E, Ferrari, P, Friesen, M, Sabate, J, Norat, T, Slimani, N, Tjonneland, A, Olsen, A, Overvad, K, Boutron-Ruault, MC, Clavel-Chapelon, F, Boeing, H, Schulz, M, Linseisen, J, Nagel, G, Trichopoulou, A, Naska, A, Oikonomou, E, Berrino, F, Panico, S, Palli, D, Sacerdote, C, Tumino, R, Peeters, PH, Numans, ME, Bueno-de Mesquita, HB, Buchner, FL, Lund, E, Pera, G, Chirlaque, MD, Sanchez, MJ, Arriola, L, Barricarte, A, Quiros, JR, Johansson, Ingegerd, Johansson, Anders, Berglund, G, Bingham, S, Khaw, KT, Allen, N, Key, T, Carneiro, F, Save, V, Del Giudice, G, Plebani, M, Kaaks, R, and Gonzalez, CA

Abstract

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and - and -tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and -tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma -cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, Ptrend=0.005) and lipid-unadjusted -tocopherol (OR=0.59, 95% CI=0.37-0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted -tocopherol (OR=0.26, 95% CI=0.11-0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and -tocopherol are associated with reduced risk of GC.

Published
2006
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41. Genetic Loci for Retinal Arteriolar Microcirculation

Author

Xueling, Sim, Jensen, Richard A., Kamran Ikram, M., Mary Frances Cotch, Xiaohui, Li, Stuart, Macgregor, Jing, Xie, Albert Vernon Smith, Eric, Boerwinkle, Paul, Mitchell, Ronald, Klein, Klein, Barbara E. K., Glazer, Nicole L., Thomas, Lumley, Barbara, Mcknight, Psaty, Bruce M., de Jong, Paulus T. V. M., Albert, Hofman, Fernando, Rivadeneira, Uitterlinden, Andre G., van Duijn, Cornelia M., Thor, Aspelund, Gudny, Eiriksdottir, Harris, Tamara B., Fridbert, Jonasson, Launer, Lenore J., John, Attia, Baird, Paul N., Stephen, Harrap, Holliday, Elizabeth G., Michael, Inouye, Elena, Rochtchina, Scott, Rodney J., Ananth, Viswanathan, Guo, Li, Smith, Nicholas L., Wiggins, Kerri L., Kuo, Jane Z., Taylor, Kent D., Hewitt, Alex W., Martin, Nicholas G., Montgomery, Grant W., Cong, Sun, Young, Terri L., Mackey, David A., van Zuydam, Natalie R., Doney, Alex S. F., Palmer, Colin N. A., Morris, Andrew D., Rotter, Jerome I., Shyong Tai, E., Vilmundur, Gudnason, Vingerling, Johannes R., Siscovick, David S., Jie Jin Wang, Wong, Tien Y., Donnelly, P, Barroso, I, Blackwell, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Mathew, C, Mccarthy, Mi, 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, Silvia, 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, 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, Simonetta, Panico, S, Ricceri, Fulvio, Romanazzi, V, Sacerdote, Carlotta, Vineis, Paolo, 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, 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, Zeleneka, D, 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, Giuseppe, 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, P. B., Inouye, Michael [0000-0001-9413-6520], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Wellcome Trust Case Control Consortium 2, Global BPGen Consortium, Donnelly, P., Barroso, I., Blackwell, J.M., Bramon, E., Brown, M.A., Casas, J.P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H.S., Mathew, C.G., Palmer, C.N., Plomin, R., Rautanen, A., Sawcer, S.J., Trembath, R.C., Viswanathan, A.C., Wood, N.W., Spencer, C.C., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Pearson, R., Strange, A., Su, Z., Vukcevic, D., Langford, C., Hunt, S.E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S.J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O.T., Liddle, J., Potter, S.C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Mathew, C., McCarthy, M.I., Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M.D., Bochud, M., Coin, L., Najjar, S.S., Zhao, J.H., Heath, S.C., Eyheramendy, S., Papadakis, K., Voight, B.F., Scott, L.J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J.C., Khaw, K.T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D.E., Onland-Moret, N.C., Bots, M.L., Wain, L.V., Elliott, K.S., Teumer, A., Luan, J.J., Lucas, G., Kuusisto, J., Burton, P.R., Hadley, D., McArdle, W.L., Brown, M., Dominiczak, A., Newhouse, S.J., Samani, N.J., Webster, J., Zeggini, E., Beckmann, J.S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D.M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Sandhu, M.S., Luben, R.N., Crawford, G.J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L.L., Collins, F.S., Jackson, A.U., Mohlke, K.L., Stringham, H.M., Valle, T.T., Willer, C.J., Bergman, R.N., Morken, M.A., Döring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H.E., Kathiresan, S., Marrugat, J., O'Donnell, C.J., Schwartz, S.M., Siscovick, D.S., Subirana, I., Freimer, N.B., Hartikainen, A.L., O'Reilly, P.F., Peltonen, L., Pouta, A., de Jong, P.E., Snieder, H., van Gilst, W.H., Clarke, R., Goel, A., Hamsten, A., Peden, J.F., Seedorf, U., Syvänen, A.C., Tognoni, G., Lakatta, E.G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dörr, M., Ernst, F., Felix, S.B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Völker, U., Galan, P., Gut, I.G., Hercberg, S., Lathrop, G.M., Zeleneka, D., Soranzo, N., Williams, F.M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N.G., Völzke, H., Uiterwaal, C.S., van der Schouw, Y.T., Numans, M.E., Matullo, G., Navis, G., Berglund, G., Bingham, S.A., Kooner, J.S., Connell, J.M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T.D., Tuomilehto, J., Altshuler, D., Strachan, D.P., Laan, M., Meneton, P., Wareham, N.J., Uda, M., Jarvelin, M.R., Mooser, V., Melander, O., Loos, R.J., Elliott, P., Abecasis, G.R., Caulfield, M., Munroe, P.B., Ophthalmology, Epidemiology, Internal Medicine, Erasmus School of Social and Behavioural Sciences, and Obstetrics & Gynecology

Subjects
Male, Pathology, BLUE MOUNTAINS EYE, VESSEL DIAMETERS, lcsh:Medicine, MICROVASCULAR ABNORMALITIES, Genome-wide association study, Cardiovascular, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, genome-wide association, Microcirculation, Retinal Arteriolar Microcirculation, Myocardial infarction, lcsh:Science, Aged, 80 and over, Medicine(all), 0303 health sciences, Multidisciplinary, Agricultural and Biological Sciences(all), MEF2 Transcription Factors, Genomics, Middle Aged, 3. Good health, Arterioles, medicine.anatomical_structure, Medicine, Chromosomes, Human, Pair 5, Female, INCIDENT SEVERE HYPERTENSION, Research Article, medicine.medical_specialty, Genotype, Clinical Research Design, ANTIHYPERTENSIVE DRUG THERAPIES, Single-nucleotide polymorphism, White People, 03 medical and health sciences, Genome Analysis Tools, Vascular Biology, BEAVER DAM EYE, Genetics, Genome-Wide Association Studies, medicine, Humans, CORONARY-HEART-DISEASE, GENOME-WIDE ASSOCIATION, Biology, Aged, 030304 developmental biology, Retina, Models, Genetic, Biochemistry, Genetics and Molecular Biology(all), Vascular disease, business.industry, lcsh:R, Computational Biology, Retinal Vessels, Human Genetics, Retinal, medicine.disease, Ophthalmology, chemistry, Genetic Loci, VASCULAR CALIBER, 030221 ophthalmology & optometry, lcsh:Q, Meta-Analyses, GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK, business, Genome-Wide Association Study
Abstract

Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value -8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10-12 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

Published
2013

45. Prediction of adverse health outcomes in older people using a frailty index based on routine primary care data.

Author

Drubbel I, de Wit NJ, Bleijenberg N, Eijkemans RJ, Schuurmans MJ, and Numans ME

Abstract

BACKGROUND: A general frailty indicator could guide general practitioners (GPs) in directing their care efforts to the patients at highest risk. We investigated if a Frailty Index (FI) based on the routine health care data of GPs can predict the risk of adverse health outcomes in community-dwelling older people. METHODS: This was a retrospective cohort study with a 2-year follow-up period among all patients in an urban primary care center aged 60 and older: 1,679 patients (987 women [59%], median age, 73 years [interquartile range, 65-81]). For each patient, a baseline FI score was computed as the number of health deficits present divided by the total number of 36 deficits on the FI. Adverse health outcomes were defined as the first registered event of an emergency department (ED) or after-hours GP visit, nursing home admission, or death. RESULTS: In total, 508 outcome events occurred within the sample population. Kaplan-Meier survival curves were constructed according to FI tertiles. The tertiles were able to discriminate between patients with low, intermediate, and high risk for adverse health outcomes (p value < .001). With adjustments for age, consultation gap, and sex, a one deficit increase in the FI score was associated with an increased hazard for adverse health outcomes (hazard ratio, 1.166; 95% confidence interval [CI], 1.129-1.210) and a moderate predictive ability for adverse health outcomes (c-statistic, 0.702; 95% CI, 0.680-0.724). CONCLUSIONS: An FI based on International Classification of Primary Care (ICPC)-encoded routine health care data does predict the risk of adverse health outcomes in elderly population. [ABSTRACT FROM AUTHOR]

Published
2013
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