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212 results on '"Jonasson, F"'

1. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Author

Seielstad, Mark, Jensen, RA, Sim, X, Li, X, Cotch, MF, Ikram, MK, Holliday, EG, Eiriksdottir, G, Harris, TB, Jonasson, F, and Klein, BEK

Abstract

Background: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in

Published
2013

20. Elevated plasma HDL-cholesterol is associated with incident early AMD and progression to geographic atrophy and not to exudative AMD

Author

Jonasson, F, Fisher, D, Eiriksdottir, G, Sigurdsson, S, Klein, R, Loner, L, Harris, T, Gudnason, V, and Cotch, MF

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: The Age, Gene/Environment Susceptibility Reykjavik Study includes a random population sample including persons 67 years and older at baseline, mean age 76 years. This is an older cohort than in most studies and therefore higher numbers of persons with late AMD (n=277), both exudative[for full text, please go to the a.m. URL], VI. International Symposium on AMD – Age-Related Macular Degeneration – Emerging Concepts – Exploring known and Identifying new Pathways

Published
2015
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21. 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

22. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Author

Springelkamp, H, Höhn, R, Mishra, A, Hysi, PG, Khor, CC, Loomis, SJ, Bailey, JNC, Gibson, J, Thorleifsson, G, Janssen, SF, Luo, X, Ramdas, WD, Vithana, E, Nongpiur, ME, Montgomery, GW, Xu, L, Mountain, JE, Gharahkhani, P, Lu, Y, Amin, N, Karssen, LC, Sim, KS, Van Leeuwen, EM, Iglesias, AI, Verhoeven, VJM, Hauser, MA, Loon, SC, Despriet, DDG, Nag, A, Venturini, C, Sanfilippo, PG, Schillert, A, Kang, JH, Landers, J, Jonasson, F, Cree, AJ, Van Koolwijk, LME, Rivadeneira, F, Souzeau, E, Jonsson, V, Menon, G, Mitchell, P, Wang, JJ, Rochtchina, E, Attia, J, Scott, R, Holliday, EG, Baird, PN, Xie, J, Inouye, M, Viswanathan, A, Sim, X, Weinreb, RN, De Jong, PTVM, Oostra, BA, Uitterlinden, AG, Hofman, A, Ennis, S, Thorsteinsdottir, U, Burdon, KP, Allingham, RR, Brilliant, MH, Budenz, DL, Christen, WG, Fingert, J, Friedman, DS, Gaasterland, D, Gaasterland, T, Haines, JL, Kraft, P, Lee, RK, Lichter, PR, and Liu, Y

Subjects
genetic structures, sense organs, eye diseases
Abstract

© 2014 Macmillan Publishers Limited. All rights reserved. Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Published
2014

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

Author

Ikram, M.K., Xueling, S., Jensen, R.A., Cotch, M.F., Hewitt, A.W., Ikram, M.A., Wang, J.J., Klein, R., Klein, B.E., Breteler, M.M., Cheung, N., Liew, G., Mitchell, P., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., de Jong, P.T.V.M., Van Duijn, C.M., Kao, L., Cheng, C.Y., Smith, A.V., Glazer, N.L., Lumley, T., McKnight, B., Psaty, B.M., Jonasson, F., Eiriksdottir, G., Aspelund, T., Global BPgen Consortium, X., and Netherlands Institute for Neuroscience (NIN)

Published
2010

24. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Author

Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Aung, T. (Tin), Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), and Aung, T. (Tin)

Abstract

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10 '8 for rs6445055), two on chromosome 9 (P = 2.80 × 10 '11 for rs2472493 near ABCA1 and P = 6.39 × 10 '11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10 '11 for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Published
2014
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25. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Author

Springelkamp, H. (Henriët), Höhn, R. (René), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Khor, C.C., Loomis, S.J. (Stephanie J.), Bailey, J.N.C. (Jessica N. Cooke), Gibson, J. (Jane), Thorleifsson, G. (Gudmar), Janssen, S.F. (Sarah), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Nongpiur, M.E. (Monisha E.), Montgomery, G.W. (Grant), Xu, L. (Liang), Mountain, J.E. (Jenny E.), Gharahkhani, P. (Puya), Lu, Y. (Yi), Amin, N. (Najaf), Karssen, L.C. (Lennart), Sim, K.S., Leeuwen, E.M. (Elisa) van, Iglesias González, A.I. (Adriana), Verhoeven, V.J.M. (Virginie), Hauser, M.A. (Michael), Loon, S.-C. (Seng-Chee), Despriet, D.D.G. (Dominique), Nag, A. (Abhishek), Venturini, C. (Cristina), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Kang, J.H. (Jae), Landers, J. (John), Jonasson, F. (Fridbert), Cree, A.J. (Angela), Koolwijk, L.M.E. (Leonieke) van, Rivadeneira Ramirez, F. (Fernando), Souzeau, E. (Emmanuelle), Jonsson, V. (Vesteinn), Menon, G. (Geeta), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A.C. (Ananth), Sim, X. (Xueling), Weinreb, R.N. (Robert N.), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Ennis, S. (Sarah), Thorsteinsdottir, U. (Unnur), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Mirshahi, A. (Alireza), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jansonius, N.M. (Nomdo), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), MacGregor, S. (Stuart), Mackey, D.A. (David), Lotery, A.J. (Andrew), Zwart, J-A. (John-Anker), Bergen, A.A.B. (Arthur), Young, T.L. (Terri), Wiggs, J.L. (Janey), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Pasquale, L.R. (Louis), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Springelkamp, H. (Henriët), Höhn, R. (René), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Khor, C.C., Loomis, S.J. (Stephanie J.), Bailey, J.N.C. (Jessica N. Cooke), Gibson, J. (Jane), Thorleifsson, G. (Gudmar), Janssen, S.F. (Sarah), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Nongpiur, M.E. (Monisha E.), Montgomery, G.W. (Grant), Xu, L. (Liang), Mountain, J.E. (Jenny E.), Gharahkhani, P. (Puya), Lu, Y. (Yi), Amin, N. (Najaf), Karssen, L.C. (Lennart), Sim, K.S., Leeuwen, E.M. (Elisa) van, Iglesias González, A.I. (Adriana), Verhoeven, V.J.M. (Virginie), Hauser, M.A. (Michael), Loon, S.-C. (Seng-Chee), Despriet, D.D.G. (Dominique), Nag, A. (Abhishek), Venturini, C. (Cristina), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Kang, J.H. (Jae), Landers, J. (John), Jonasson, F. (Fridbert), Cree, A.J. (Angela), Koolwijk, L.M.E. (Leonieke) van, Rivadeneira Ramirez, F. (Fernando), Souzeau, E. (Emmanuelle), Jonsson, V. (Vesteinn), Menon, G. (Geeta), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A.C. (Ananth), Sim, X. (Xueling), Weinreb, R.N. (Robert N.), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Ennis, S. (Sarah), Thorsteinsdottir, U. (Unnur), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Mirshahi, A. (Alireza), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jansonius, N.M. (Nomdo), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), MacGregor, S. (Stuart), Mackey, D.A. (David), Lotery, A.J. (Andrew), Zwart, J-A. (John-Anker), Bergen, A.A.B. (Arthur), Young, T.L. (Terri), Wiggs, J.L. (Janey), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Pasquale, L.R. (Louis), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, and Hammond, C.J. (Christopher)

Abstract

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Published
2014
Full Text
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26. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Author

Hysi, PG, Cheng, C-Y, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Hohn, R, Venturini, C, Mirshahi, A, Ramdas, WD, Thorleifsson, G, Vithana, E, Khor, C-C, Stefansson, AB, Liao, J, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, Y-Y, Cuellar-Partida, G, Luo, X, Allingham, RR, Richards, JE, Senft, A, Karssen, LC, Zheng, Y, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, van Leeuwen, EM, Jonsson, V, Thorsteinsdottir, U, Despriet, DDG, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, Yazar, S, Tai, E-S, Amouyel, P, Kirwan, J, van Koolwijk, LME, Hauser, MA, Jonasson, F, Leo, P, Loomis, SJ, Fogarty, R, Rivadeneira, F, Kearns, L, Lackner, KJ, de Jong, PTVM, Simpson, CL, Pennell, CE, Oostra, BA, Uitterlinden, AG, Saw, S-M, Lotery, AJ, Bailey-Wilson, JE, Hofman, A, Vingerling, JR, Maubaret, C, Pfeiffer, N, Wolfs, RCW, Lemij, HG, Young, TL, Pasquale, LR, Delcourt, C, Spector, TD, Klaver, CCW, Small, KS, Burdon, KP, Stefansson, K, Wong, T-Y, Viswanathan, A, Mackey, DA, Craig, JE, Wiggs, JL, van Duijn, CM, Hammond, CJ, Aung, T, Hysi, PG, Cheng, C-Y, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Hohn, R, Venturini, C, Mirshahi, A, Ramdas, WD, Thorleifsson, G, Vithana, E, Khor, C-C, Stefansson, AB, Liao, J, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, Y-Y, Cuellar-Partida, G, Luo, X, Allingham, RR, Richards, JE, Senft, A, Karssen, LC, Zheng, Y, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, van Leeuwen, EM, Jonsson, V, Thorsteinsdottir, U, Despriet, DDG, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, Yazar, S, Tai, E-S, Amouyel, P, Kirwan, J, van Koolwijk, LME, Hauser, MA, Jonasson, F, Leo, P, Loomis, SJ, Fogarty, R, Rivadeneira, F, Kearns, L, Lackner, KJ, de Jong, PTVM, Simpson, CL, Pennell, CE, Oostra, BA, Uitterlinden, AG, Saw, S-M, Lotery, AJ, Bailey-Wilson, JE, Hofman, A, Vingerling, JR, Maubaret, C, Pfeiffer, N, Wolfs, RCW, Lemij, HG, Young, TL, Pasquale, LR, Delcourt, C, Spector, TD, Klaver, CCW, Small, KS, Burdon, KP, Stefansson, K, Wong, T-Y, Viswanathan, A, Mackey, DA, Craig, JE, Wiggs, JL, van Duijn, CM, Hammond, CJ, and Aung, T

Abstract

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Published
2014

27. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Author

Springelkamp, Henriët, Hohn, R, Mishra, A, Hysi, PG, Khor, CC, Loomis, SJ, Bailey, JNC, Gibson, J, Thorleifsson, G, Janssen, SF, Luo, XY, Ramdas, Wishal, Vithana, E, Nongpiur, ME, Montgomery, G, Xu, L, Mountain, JE, Gharahkhani, P, Lu, Y (Yi), Amin, Najaf, Karssen, Lennart, Sim, KS, Leeuwen, Elisa, Iglesias, AI, Verhoeven, Virginie, Hauser, MA, Loon, SC, Despriet, Dominiek, Nag, A, Venturini, C, Sanfilippo, PG, Schillert, A, Kang, JH, Landers, J, Jonasson, F, Cree, AJ, Koolwijk, Leonieke, Rivadeneira, Fernando, Souzeau, E, Jonsson, V, Menon, G, Weinreb, RN, Oostra, Ben, Uitterlinden, André, Hofman, Bert, Ennis, S, Thorsteinsdottir, U, Burdon, KP, Spector, TD, Mirshahi, A, Saw, SM, Vingerling, Hans, Teo, YY, Haines, JL, Wolfs, R.C.W., Lemij, HG, Tai, ES, Jansonius, NM (Nomdo), Jonas, JB, Cheng, CY (Ching-Yu), Aung, T, Viswanathan, AC, Klaver, Caroline, Craig, JE, Macgregor, S, Mackey, DA, Lotery, AJ, Stefansson, K, Young, TL, Wiggs, JL, Pfeiffer, N, Wong, TY (Tien Yin), Pasquale, LR, Hewitt, AW, Duijn, Cornelia, Hammond, CJ, Bergen, AAB, Springelkamp, Henriët, Hohn, R, Mishra, A, Hysi, PG, Khor, CC, Loomis, SJ, Bailey, JNC, Gibson, J, Thorleifsson, G, Janssen, SF, Luo, XY, Ramdas, Wishal, Vithana, E, Nongpiur, ME, Montgomery, G, Xu, L, Mountain, JE, Gharahkhani, P, Lu, Y (Yi), Amin, Najaf, Karssen, Lennart, Sim, KS, Leeuwen, Elisa, Iglesias, AI, Verhoeven, Virginie, Hauser, MA, Loon, SC, Despriet, Dominiek, Nag, A, Venturini, C, Sanfilippo, PG, Schillert, A, Kang, JH, Landers, J, Jonasson, F, Cree, AJ, Koolwijk, Leonieke, Rivadeneira, Fernando, Souzeau, E, Jonsson, V, Menon, G, Weinreb, RN, Oostra, Ben, Uitterlinden, André, Hofman, Bert, Ennis, S, Thorsteinsdottir, U, Burdon, KP, Spector, TD, Mirshahi, A, Saw, SM, Vingerling, Hans, Teo, YY, Haines, JL, Wolfs, R.C.W., Lemij, HG, Tai, ES, Jansonius, NM (Nomdo), Jonas, JB, Cheng, CY (Ching-Yu), Aung, T, Viswanathan, AC, Klaver, Caroline, Craig, JE, Macgregor, S, Mackey, DA, Lotery, AJ, Stefansson, K, Young, TL, Wiggs, JL, Pfeiffer, N, Wong, TY (Tien Yin), Pasquale, LR, Hewitt, AW, Duijn, Cornelia, Hammond, CJ, and Bergen, AAB

Abstract

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Published
2014

28. A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration

Author

Helgason, H., Sulem, P., Duvvari, M.R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D.F., Walters, G.B., Magnusson, O.T., Kong, A., Rafnar, T., Kiemeney, L.A.L.M., Schoenmaker-Koller, F.E., Zhao, L., Boon, C.J.F., Song, Y., Fauser, S., Pei, M., Ristau, T., Patel, S., Liakopoulos, S., Ven, J.P.H. van de, Hoyng, C.B., Ferreyra, H., Duan, Y., Bernstein, P.S., Geirsdottir, A., Helgadottir, G., Stefansson, E., Hollander, A.I. den, Zhang, K., Jonasson, F., Sigurdsson, H., Thorsteinsdottir, U., Stefansson, K., Helgason, H., Sulem, P., Duvvari, M.R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D.F., Walters, G.B., Magnusson, O.T., Kong, A., Rafnar, T., Kiemeney, L.A.L.M., Schoenmaker-Koller, F.E., Zhao, L., Boon, C.J.F., Song, Y., Fauser, S., Pei, M., Ristau, T., Patel, S., Liakopoulos, S., Ven, J.P.H. van de, Hoyng, C.B., Ferreyra, H., Duan, Y., Bernstein, P.S., Geirsdottir, A., Helgadottir, G., Stefansson, E., Hollander, A.I. den, Zhang, K., Jonasson, F., Sigurdsson, H., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 125275.pdf (publisher's version ) (Closed access), Through whole-genome sequencing of 2,230 Icelanders, we detected a rare nonsynonymous SNP (minor allele frequency = 0.55%) in the C3 gene encoding a p.Lys155Gln substitution in complement factor 3, which, following imputation into a set of Icelandic cases with age-related macular degeneration (AMD) and controls, associated with disease (odds ratio (OR) = 3.45; P = 1.1 x 10(-7)). This signal is independent of the previously reported common SNPs in C3 encoding p.Pro314Leu and p.Arg102Gly that associate with AMD. The association of p.Lys155Gln was replicated in AMD case-control samples of European ancestry with OR = 4.22 and P = 1.6 x 10(-10), resulting in OR = 3.65 and P = 8.8 x 10(-16) for all studies combined. In vitro studies have suggested that the p.Lys155Gln substitution reduces C3b binding to complement factor H, potentially creating resistance to inhibition by this factor. This resistance to inhibition in turn is predicted to result in enhanced complement activation.

Published
2013

29. Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

Author

Holliday, E.G. (Elizabeth), Smith, A.V. (Davey), Cornes, B.K. (Belinda), Buitendijk, G.H.S. (Gabrielle), Jensen, R.A. (Richard), Sim, X. (Xueling), Aspelund, T. (Thor), Aung, T. (Tin), Baird, P.N. (Paul), Boerwinkle, E.A. (Eric), Cheng, C-Y. (Ching-Yu), Duijn, C.M. (Cornelia) van, Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hewit, A.W. (Alex), Inouye, M. (Michael), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Li, X. (Xiaohui), Liew, G. (Gerald), Lumley, T. (Thomas), McElduff, P. (Patrick), McKnight, B. (Barbara), Mitchell, P. (Paul), Psaty, B.M. (Bruce), Rochtchina, E. (Elena), Rotter, J.I. (Jerome), Scott, R.J. (Rodney), Tay, W.-T. (Wan-Ting), Taylor, K. (Kent), Teo, Y.Y. (Yik Ying), Uitterlinden, A.G. (André), Viswanathan, A. (Anand), Xie, S. (Sophia), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Tai, E.S. (Shyong), Siscovick, D.S. (David), Klein, R. (Ronald), Cotch, M.F. (Mary Frances), Wong, T.Y. (Tien Yin), Attia, J. (John), Wang, J.J. (Jie Jin), Holliday, E.G. (Elizabeth), Smith, A.V. (Davey), Cornes, B.K. (Belinda), Buitendijk, G.H.S. (Gabrielle), Jensen, R.A. (Richard), Sim, X. (Xueling), Aspelund, T. (Thor), Aung, T. (Tin), Baird, P.N. (Paul), Boerwinkle, E.A. (Eric), Cheng, C-Y. (Ching-Yu), Duijn, C.M. (Cornelia) van, Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hewit, A.W. (Alex), Inouye, M. (Michael), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Li, X. (Xiaohui), Liew, G. (Gerald), Lumley, T. (Thomas), McElduff, P. (Patrick), McKnight, B. (Barbara), Mitchell, P. (Paul), Psaty, B.M. (Bruce), Rochtchina, E. (Elena), Rotter, J.I. (Jerome), Scott, R.J. (Rodney), Tay, W.-T. (Wan-Ting), Taylor, K. (Kent), Teo, Y.Y. (Yik Ying), Uitterlinden, A.G. (André), Viswanathan, A. (Anand), Xie, S. (Sophia), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Tai, E.S. (Shyong), Siscovick, D.S. (David), Klein, R. (Ronald), Cotch, M.F. (Mary Frances), Wong, T.Y. (Tien Yin), Attia, J. (John), and Wang, J.J. (Jie Jin)

Published
2013
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30. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Author

Jensen, R.A. (Richard), Sim, X. (Xueling), Li, X. (Xiaohui), Cotch, M.F. (Mary Frances), Ikram, M.K. (Kamran), Holliday, E.G. (Elizabeth), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Cheung, N. (Ning), Hewit, A.W. (Alex), Liew, G. (Gerald), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Attia, J. (John), Scott, R.J. (Rodney), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K. (Kent), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Tay, W.-T. (Wan-Ting), Teo, Y.Y. (Yik Ying), Seielstad, M. (Mark), Liu, J. (Jianjun), Cheng, C-Y. (Ching-Yu), Saw, S-M. (Seang-Mei), Aung, T. (Tin), Ganesh, S.K. (Santhi), O'Donnell, C.J. (Christopher), Nalls, M.A. (Michael), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Duijn, C.M. (Cornelia) van, Gudnason, V. (Vilmundur), Klein, R. (Ronald), Siscovick, D.S. (David), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Vingerling, J.R. (Hans), Wong, T.Y. (Tien Yin), Jensen, R.A. (Richard), Sim, X. (Xueling), Li, X. (Xiaohui), Cotch, M.F. (Mary Frances), Ikram, M.K. (Kamran), Holliday, E.G. (Elizabeth), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Cheung, N. (Ning), Hewit, A.W. (Alex), Liew, G. (Gerald), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Attia, J. (John), Scott, R.J. (Rodney), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K. (Kent), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Tay, W.-T. (Wan-Ting), Teo, Y.Y. (Yik Ying), Seielstad, M. (Mark), Liu, J. (Jianjun), Cheng, C-Y. (Ching-Yu), Saw, S-M. (Seang-Mei), Aung, T. (Tin), Ganesh, S.K. (Santhi), O'Donnell, C.J. (Christopher), Nalls, M.A. (Michael), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Duijn, C.M. (Cornelia) van, Gudnason, V. (Vilmundur), Klein, R. (Ronald), Siscovick, D.S. (David), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Vingerling, J.R. (Hans), and Wong, T.Y. (Tien Yin)

Abstract

Background: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes. Methods: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. Results: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, 21.360.23 (beta 6 standard error), p=6.661029. Evidence suggests this was a false positive finding. The minor allele frequency was low (,2%), the quality of the imputation was moderate (r2 ,0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. Conclusions: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

Published
2013
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31. Genetic Loci for Retinal Arteriolar Microcirculation

Author

Sim, X. (Xueling), Jensen, R.A. (Richard), Ikram, M.K. (Kamran), Cotch, M.F. (Mary Frances), Li, X. (Xiaohui), MacGregor, S. (Stuart), Xie, J. (Jing), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Mitchell, P. (Paul), Klein, R. (Ronald), Klein, B.E.K. (Barbara), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Launer, L.J. (Lenore), Attia, J. (John), Baird, P.N. (Paul), Harrap, S. (Stephen), Holliday, E.G. (Elizabeth), Inouye, M. (Michael), Rochtchina, E. (Elena), Scott, R.J. (Rodney), Viswanathan, A.C. (Ananth), Li, G. (Guo), Smith, N.L. (Nicholas), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Taylor, K.D. (Kent), Hewit, A.W. (Alex), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Sun, C. (Cong), Young, T.L. (Terri), Mackey, D.A. (David), Zuydam, N.R. (Natalie) van, Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Vingerling, J.R. (Hans), Siscovick, D.S. (David), Wang, J.J. (Jie Jin), Wong, T.Y. (Tien Yin), Sim, X. (Xueling), Jensen, R.A. (Richard), Ikram, M.K. (Kamran), Cotch, M.F. (Mary Frances), Li, X. (Xiaohui), MacGregor, S. (Stuart), Xie, J. (Jing), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Mitchell, P. (Paul), Klein, R. (Ronald), Klein, B.E.K. (Barbara), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Launer, L.J. (Lenore), Attia, J. (John), Baird, P.N. (Paul), Harrap, S. (Stephen), Holliday, E.G. (Elizabeth), Inouye, M. (Michael), Rochtchina, E. (Elena), Scott, R.J. (Rodney), Viswanathan, A.C. (Ananth), Li, G. (Guo), Smith, N.L. (Nicholas), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Taylor, K.D. (Kent), Hewit, A.W. (Alex), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Sun, C. (Cong), Young, T.L. (Terri), Mackey, D.A. (David), Zuydam, N.R. (Natalie) van, Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Vingerling, J.R. (Hans), Siscovick, D.S. (David), Wang, J.J. (Jie Jin), and Wong, T.Y. (Tien Yin)

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 < 5 x 10(-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 x 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, myoca

Published
2013
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32. Genetic Loci for Retinal Arteriolar Microcirculation

Author

Wallace, GR, Sim, X, Jensen, RA, Ikram, MK, Cotch, MF, Li, X, MacGregor, S, Xie, J, Smith, AV, Boerwinkle, E, Mitchell, P, Klein, R, Klein, BEK, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, de Jong, PTVM, Hofman, A, Rivadeneira, F, Uitterlinden, AG, van Duijn, CM, Aspelund, T, Eiriksdottir, G, Harris, TB, Jonasson, F, Launer, LJ, Attia, J, Baird, PN, Harrap, S, Holliday, EG, Inouye, M, Rochtchina, E, Scott, RJ, Viswanathan, A, Li, G, Smith, NL, Wiggins, KL, Kuo, JZ, Taylor, KD, Hewitt, AW, Martin, NG, Montgomery, GW, Sun, C, Young, TL, Mackey, DA, van Zuydam, NR, Doney, ASF, Palmer, CNA, Morris, AD, Rotter, JI, Tai, ES, Gudnason, V, Vingerling, JR, Siscovick, DS, Wang, JJ, Wong, TY, Wallace, GR, Sim, X, Jensen, RA, Ikram, MK, Cotch, MF, Li, X, MacGregor, S, Xie, J, Smith, AV, Boerwinkle, E, Mitchell, P, Klein, R, Klein, BEK, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, de Jong, PTVM, Hofman, A, Rivadeneira, F, Uitterlinden, AG, van Duijn, CM, Aspelund, T, Eiriksdottir, G, Harris, TB, Jonasson, F, Launer, LJ, Attia, J, Baird, PN, Harrap, S, Holliday, EG, Inouye, M, Rochtchina, E, Scott, RJ, Viswanathan, A, Li, G, Smith, NL, Wiggins, KL, Kuo, JZ, Taylor, KD, Hewitt, AW, Martin, NG, Montgomery, GW, Sun, C, Young, TL, Mackey, DA, van Zuydam, NR, Doney, ASF, Palmer, CNA, Morris, AD, Rotter, JI, Tai, ES, Gudnason, V, Vingerling, JR, Siscovick, DS, Wang, JJ, and Wong, TY

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 <5×10(-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

33. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Author

Mittal, B, Jensen, RA, Sim, X, Li, X, Cotch, MF, Ikram, MK, Holliday, EG, Eiriksdottir, G, Harris, TB, Jonasson, F, Klein, BEK, Launer, LJ, Smith, AV, Boerwinkle, E, Cheung, N, Hewitt, AW, Liew, G, Mitchell, P, Wang, JJ, Attia, J, Scott, R, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Taylor, K, Hofman, A, de Jong, PTVM, Rivadeneira, F, Uitterlinden, AG, Tay, W-T, Teo, YY, Seielstad, M, Liu, J, Cheng, C-Y, Saw, S-M, Aung, T, Ganesh, SK, O'Donnell, CJ, Nalls, MA, Wiggins, KL, Kuo, JZ, van Duijn, CM, Gudnason, V, Klein, R, Siscovick, DS, Rotter, JI, Tai, ES, Vingerling, J, Wong, TY, Mittal, B, Jensen, RA, Sim, X, Li, X, Cotch, MF, Ikram, MK, Holliday, EG, Eiriksdottir, G, Harris, TB, Jonasson, F, Klein, BEK, Launer, LJ, Smith, AV, Boerwinkle, E, Cheung, N, Hewitt, AW, Liew, G, Mitchell, P, Wang, JJ, Attia, J, Scott, R, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Taylor, K, Hofman, A, de Jong, PTVM, Rivadeneira, F, Uitterlinden, AG, Tay, W-T, Teo, YY, Seielstad, M, Liu, J, Cheng, C-Y, Saw, S-M, Aung, T, Ganesh, SK, O'Donnell, CJ, Nalls, MA, Wiggins, KL, Kuo, JZ, van Duijn, CM, Gudnason, V, Klein, R, Siscovick, DS, Rotter, JI, Tai, ES, Vingerling, J, and Wong, TY

Abstract

BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes. METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error), p = 6.6×10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r(2) ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

Published
2013

34. Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

Author

Jensen, RA, Sim, XL, Li, XH, Cotch, MF, Ikram, Kamran, Holliday, EG, Eiriksdottir, G, Harris, TB, Jonasson, F, Klein, BEK, Launer, LJ (Lenore), Smith, AV, Boerwinkle, E, Cheung, N, Hewitt, AW, Liew, G, Mitchell, P, Wang, JJ, Attia, J, Scott, R, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Taylor, K, Hofman, Bert, de Jong, PTVM (Paulus), Rivadeneira, Fernando, Uitterlinden, André, Tay, WT, Teo, YY, Seielstad, M, Liu, JJ, Cheng, CY (Ching-Yu), Saw, SM, Aung, T, Ganesh, SK, O'Donnell, CJ, Nalls, MA, Wiggins, KL, Kuo, JZ, Duijn, Cornelia, Gudnason, V, Klein, R, Siscovick, DS, Rotter, JI, Tai, ES, Vingerling, Hans, Wong, TY (Tien Yin), Jensen, RA, Sim, XL, Li, XH, Cotch, MF, Ikram, Kamran, Holliday, EG, Eiriksdottir, G, Harris, TB, Jonasson, F, Klein, BEK, Launer, LJ (Lenore), Smith, AV, Boerwinkle, E, Cheung, N, Hewitt, AW, Liew, G, Mitchell, P, Wang, JJ, Attia, J, Scott, R, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Taylor, K, Hofman, Bert, de Jong, PTVM (Paulus), Rivadeneira, Fernando, Uitterlinden, André, Tay, WT, Teo, YY, Seielstad, M, Liu, JJ, Cheng, CY (Ching-Yu), Saw, SM, Aung, T, Ganesh, SK, O'Donnell, CJ, Nalls, MA, Wiggins, KL, Kuo, JZ, Duijn, Cornelia, Gudnason, V, Klein, R, Siscovick, DS, Rotter, JI, Tai, ES, Vingerling, Hans, and Wong, TY (Tien Yin)

Published
2013

35. Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

Author

Holliday, EG, Smith, AV, Cornes, BK, Buitendijk, Gabriëlle, Jensen, RA, Sim, XL, Aspelund, T, Aung, T, Baird, PN, Boerwinkle, E, Cheng, CY (Ching-Yu), Duijn, Cornelia, Eiriksdottir, G, Gudnason, V, Harris, T, Hewitt, AW, Inouye, M, Jonasson, F, Klein, BEK, Launer, L, Li, XH, Liew, G, Lumley, T, McElduff, P, McKnight, B, Mitchell, P, Psaty, BM, Rochtchina, E, Rotter, JI, Scott, RJ, Tay, WT, Taylor, K, Teo, YY, Uitterlinden, André, Viswanathan, A, Xie, SY, Vingerling, Hans, Klaver, Caroline, Tai, ES, Siscovick, D, Klein, R, Cotch, MF, Wong, TY (Tien Yin), Attia, J, Wang, JJ, Holliday, EG, Smith, AV, Cornes, BK, Buitendijk, Gabriëlle, Jensen, RA, Sim, XL, Aspelund, T, Aung, T, Baird, PN, Boerwinkle, E, Cheng, CY (Ching-Yu), Duijn, Cornelia, Eiriksdottir, G, Gudnason, V, Harris, T, Hewitt, AW, Inouye, M, Jonasson, F, Klein, BEK, Launer, L, Li, XH, Liew, G, Lumley, T, McElduff, P, McKnight, B, Mitchell, P, Psaty, BM, Rochtchina, E, Rotter, JI, Scott, RJ, Tay, WT, Taylor, K, Teo, YY, Uitterlinden, André, Viswanathan, A, Xie, SY, Vingerling, Hans, Klaver, Caroline, Tai, ES, Siscovick, D, Klein, R, Cotch, MF, Wong, TY (Tien Yin), Attia, J, and Wang, JJ

Published
2013

36. Genetic Loci for Retinal Arteriolar Microcirculation

Author

Sim, X, Jensen, RA, Ikram, Kamran, Cotch, MF, Li, XH, Macgregor, S, Xie, J, Smith, AV, Boerwinkle, E, Mitchell, P, Klein, R, Klein, BEK, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, de Jong, PTVM (Paulus), Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Duijn, Cornelia, Aspelund, T, Eiriksdottir, G, Harris, TB, Jonasson, F, Launer, LJ (Lenore), Attia, J, Baird, PN, Harrap, S, Holliday, EG, Inouye, M, Rochtchina, E, Scott, RJ, Viswanathan, A, Li, G (Guo), Smith, NL, Wiggins, KL, Kuo, JZ, Taylor, KD, Hewitt, AW, Martin, NG, Montgomery, GW, Sun, C, Young, TL, Mackey, DA, van Zuydam, NR, Doney, ASF, Palmer, CNA, Morris, AD, Rotter, JI, Tai, ES, Gudnason, V, Vingerling, Hans, Siscovick, DS, Wang, JJ, Wong, TY (Tien Yin), Sim, X, Jensen, RA, Ikram, Kamran, Cotch, MF, Li, XH, Macgregor, S, Xie, J, Smith, AV, Boerwinkle, E, Mitchell, P, Klein, R, Klein, BEK, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, de Jong, PTVM (Paulus), Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Duijn, Cornelia, Aspelund, T, Eiriksdottir, G, Harris, TB, Jonasson, F, Launer, LJ (Lenore), Attia, J, Baird, PN, Harrap, S, Holliday, EG, Inouye, M, Rochtchina, E, Scott, RJ, Viswanathan, A, Li, G (Guo), Smith, NL, Wiggins, KL, Kuo, JZ, Taylor, KD, Hewitt, AW, Martin, NG, Montgomery, GW, Sun, C, Young, TL, Mackey, DA, van Zuydam, NR, Doney, ASF, Palmer, CNA, Morris, AD, Rotter, JI, Tai, ES, Gudnason, V, Vingerling, Hans, Siscovick, DS, Wang, JJ, and Wong, TY (Tien Yin)

Published
2013

37. Common genetic variants associated with open-angle glaucoma.

Author

Ramdas, W.D., van Koolwijk, L.M., Lemij, H.G., Pasutto, F., Cree, A.J., Thorleifsson, G., Janssen, S.F., Jacoline, T.B., Amin, N., Rivadeneira, F., Wolfs, R.C., Walters, G.B., Jonasson, F., Weisschuh, N., Mardin, C.Y., Gibson, J., Zegers, R.H., Hofman, A., de Jong, P.T.V.M., Uitterlinden, A.G., Oostra, B.A., Thorsteinsdottir, U., Gramer, E., Welgen-Lussen, U.C., Kirwan, J.F., Bergen, A.A.B., Reis, A., Stefansson, K., Lotery, A.J., Vingerling, J.R., Jansonius, N.M., Klaver, C.C., Van Duijn, C.M., Ramdas, W.D., van Koolwijk, L.M., Lemij, H.G., Pasutto, F., Cree, A.J., Thorleifsson, G., Janssen, S.F., Jacoline, T.B., Amin, N., Rivadeneira, F., Wolfs, R.C., Walters, G.B., Jonasson, F., Weisschuh, N., Mardin, C.Y., Gibson, J., Zegers, R.H., Hofman, A., de Jong, P.T.V.M., Uitterlinden, A.G., Oostra, B.A., Thorsteinsdottir, U., Gramer, E., Welgen-Lussen, U.C., Kirwan, J.F., Bergen, A.A.B., Reis, A., Stefansson, K., Lotery, A.J., Vingerling, J.R., Jansonius, N.M., Klaver, C.C., and Van Duijn, C.M.

Published
2011

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

Author

Ikram, M.K. (Kamran), Xueling, S. (Sim), Jensen, R.A. (Richard), Cotch, M.F. (Mary Frances), Hewit, A.W. (Alex), Ikram, M.A. (Arfan), Wang, J.J. (Jie Jin), Klein, B.E.K. (Barbara), Breteler, M.M.B. (Monique), Cheung, N. (Ning), Liew, G. (Gerald), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Duijn, C.M. (Cornelia) van, Kao, L. (Linda), Cheng, C-Y. (Ching-Yu), Smith, A.V. (Albert Vernon), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jonasson, F. (Fridbert), Eiriksdottir, G. (Gudny), Aspelund, T. (Thor), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Taylor, K.D. (Kent), Li, X. (Xiaohui), Sivakumaran, T.A. (Theru), Mackey, D.A. (David), MacGregor, S. (Stuart), Martin, N.G. (Nicholas), Young, T.L. (Terry), Bis, J.C. (Joshua), Wiggins, K.L. (Kerri), Heckbert, S.R. (Susan), Hammond, C.J. (Christopher), Andrew, T. (Toby), Fahy, S. (Samantha), Attia, J. (John), Holliday, E.G. (Elizabeth), Scott, R.J. (Rodney), Islam, F.M.A. (Amirul), Rotter, J.I. (Jerome), McAuley, A.K. (Annie), Boerwinkle, E.A. (Eric), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Vingerling, J.R. (Hans), Wong, T.Y. (Tien Yin), Ikram, M.K. (Kamran), Xueling, S. (Sim), Jensen, R.A. (Richard), Cotch, M.F. (Mary Frances), Hewit, A.W. (Alex), Ikram, M.A. (Arfan), Wang, J.J. (Jie Jin), Klein, B.E.K. (Barbara), Breteler, M.M.B. (Monique), Cheung, N. (Ning), Liew, G. (Gerald), Mitchell, P. (Paul), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Jong, P.T.V.M. (Paulus) de, Duijn, C.M. (Cornelia) van, Kao, L. (Linda), Cheng, C-Y. (Ching-Yu), Smith, A.V. (Albert Vernon), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jonasson, F. (Fridbert), Eiriksdottir, G. (Gudny), Aspelund, T. (Thor), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Taylor, K.D. (Kent), Li, X. (Xiaohui), Sivakumaran, T.A. (Theru), Mackey, D.A. (David), MacGregor, S. (Stuart), Martin, N.G. (Nicholas), Young, T.L. (Terry), Bis, J.C. (Joshua), Wiggins, K.L. (Kerri), Heckbert, S.R. (Susan), Hammond, C.J. (Christopher), Andrew, T. (Toby), Fahy, S. (Samantha), Attia, J. (John), Holliday, E.G. (Elizabeth), Scott, R.J. (Rodney), Islam, F.M.A. (Amirul), Rotter, J.I. (Jerome), McAuley, A.K. (Annie), Boerwinkle, E.A. (Eric), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Vingerling, J.R. (Hans), and Wong, T.Y. (Tien Yin)

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<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

Published
2010
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39. Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo

Author

McCarthy, MI, Ikram, MK, Xueling, S, Jensen, RA, Cotch, MF, Hewitt, AW, Ikram, MA, Wang, JJ, Klein, R, Klein, BEK, Breteler, MMB, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, AG, Rivadeneira, F, Hofman, A, de Jong, PTVM, van Duijn, CM, Kao, L, Cheng, C-Y, Smith, AV, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Jonasson, F, Eiriksdottir, G, Aspelund, T, 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, FMA, Rotter, JI, McAuley, AK, Boerwinkle, E, Tai, ES, Gudnason, V, Siscovick, DS, Vingerling, JR, Wong, TY, McCarthy, MI, Ikram, MK, Xueling, S, Jensen, RA, Cotch, MF, Hewitt, AW, Ikram, MA, Wang, JJ, Klein, R, Klein, BEK, Breteler, MMB, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, AG, Rivadeneira, F, Hofman, A, de Jong, PTVM, van Duijn, CM, Kao, L, Cheng, C-Y, Smith, AV, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Jonasson, F, Eiriksdottir, G, Aspelund, T, 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, FMA, Rotter, JI, McAuley, AK, Boerwinkle, E, Tai, ES, Gudnason, V, Siscovick, DS, Vingerling, JR, and Wong, TY

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<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

Published
2010

40. Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo

Author

Ikram, Kamran, Xueling, S, Jensen, RA, Cotch, MF, Hewitt, AW, Ikram, Arfan, Wang, JJ, Klein, R, Klein, BEK, Breteler, Monique, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, André, Rivadeneira, Fernando, Hofman, Bert, de Jong, PTVM (Paulus), Duijn, Cornelia, Kao, L, Cheng, CY (Ching-Yu), Smith, AV, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Jonasson, F, Eiriksdottir, G, Aspelund, T, Harris, TB, Launer, LJ (Lenore), Taylor, KD, Li, XH, Iyengar, SK, Xi, QS, 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, FMA, Rotter, JI, McAuley, AK, Boerwinkle, E, Tai, ES, Gudnason, V, Siscovick, DS, Vingerling, Hans, Wong, TY, Ikram, Kamran, Xueling, S, Jensen, RA, Cotch, MF, Hewitt, AW, Ikram, Arfan, Wang, JJ, Klein, R, Klein, BEK, Breteler, Monique, Cheung, N, Liew, G, Mitchell, P, Uitterlinden, André, Rivadeneira, Fernando, Hofman, Bert, de Jong, PTVM (Paulus), Duijn, Cornelia, Kao, L, Cheng, CY (Ching-Yu), Smith, AV, Glazer, NL, Lumley, T, McKnight, B, Psaty, BM, Jonasson, F, Eiriksdottir, G, Aspelund, T, Harris, TB, Launer, LJ (Lenore), Taylor, KD, Li, XH, Iyengar, SK, Xi, QS, 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, FMA, Rotter, JI, McAuley, AK, Boerwinkle, E, Tai, ES, Gudnason, V, Siscovick, DS, Vingerling, Hans, and Wong, TY

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<5.0x10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61x10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25x10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15x10(-13), in the region of ATXN2, SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32x10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

Published
2010

41. Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study

Author

Fisher, D., primary, Li, C.-M., additional, Chiu, M. S., additional, Themann, C. L., additional, Petersen, H., additional, Jonasson, F., additional, Jonsson, P. V., additional, Sverrisdottir, J. E., additional, Garcia, M., additional, Harris, T. B., additional, Launer, L. J., additional, Eiriksdottir, G., additional, Gudnason, V., additional, Hoffman, H. J., additional, and Cotch, M. F., additional

Published
2013
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42. Genetic determinants of hair, eye and skin pigmentation in Europeans.

Author

Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Magnusson, K.P., Manolescu, A., Karason, A., Palsson, A., Thorleifsson, G., Jakobsdottir, M., Steinberg, S., Palsson, S., Jonasson, F., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., Stefansson, K., Sulem, P., Gudbjartsson, D.F., Stacey, S.N., Helgason, A., Rafnar, T., Magnusson, K.P., Manolescu, A., Karason, A., Palsson, A., Thorleifsson, G., Jakobsdottir, M., Steinberg, S., Palsson, S., Jonasson, F., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Aben, K.K.H., Kiemeney, L.A.L.M., Olafsson, J.H., Gulcher, J.R., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 51715.pdf (publisher's version ) (Closed access), Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.

Published
2007

43. Linkage of a gene for macular corneal dystrophy to chromosome 16

Author

Vance, J. M., Jonasson, F., Lennon, F., Sarrica, J., Damji, K. F., Stauffer, J., Pericak-Vance, M. A., and Klintworth, G. K.

Subjects
Corneal Dystrophies, Hereditary, Male, genetic structures, Genetic Linkage, Iceland, nutritional and metabolic diseases, eye diseases, Pedigree, Genetic Heterogeneity, Humans, Female, Americas, Chromosomes, Human, Pair 16, Research Article
Abstract

Autosomal recessive macular corneal dystrophy (MCD) is a heterogeneous disorder leading to visual impairment. Sixteen American and Icelandic families (11 type I and 5 type II) were analyzed for linkage, by use of 208 polymorphic microsatellite markers. A significant maximum LOD score Zmax of 7.82 at a maximum recombination fraction (thetamax) of .06 was found with the 16q22 locus D16S518 for MCD type I. In addition, a peak LOD score of 2.50 at a recombination fraction of .00 was obtained for the MCD type II families, by use of the identical marker. These findings raise the possibility that MCD type II may be due to the same genetic locus that is involved in MCD type I.

Published
1996

44. Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R)

Author

Gunnlaugsdottir, E., primary, Halldorsdottir, S., additional, Klein, R., additional, Eiriksdottir, G., additional, Klein, B. E., additional, Benediktsson, R., additional, Harris, T. B., additional, Launer, L. J., additional, Aspelund, T., additional, Gudnason, V., additional, Cotch, M. F., additional, and Jonasson, F., additional

Published
2011
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