Research Biographies

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PROFESSOR ALAN WRIGHT FRCP FRSE FMedSci

Medical and Developmental Genetics

Programme Leader


Professor Alan Wright

Contact Details

E-mail address: alan.wright@hgu.mrc.ac.uk
Telephone: +44 (0)131 332 2471 (extension 2427)
Fax: +44 (0)131 467 8456
Address: Medical Research Council
Human Genetics Unit
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
Research Programme 1: Retinal Degeneration Programme
Research Programme 2: Quantitative Trait Locus (QTL) Identification in Isolate Populations

 

 

Research Areas

Retinal Degeneration Programme

Summary and Purpose

The aims of this programme are to identify and characterise genes involved in human retinal degeneration, to understand disease mechanisms and to work towards effective therapies. We are currently focusing on the functions of two genes that cause retinitis pigmentosa (RPGR) and late-onset macular degeneration (C1QTNF5) respectively. We have developed mouse models for both types of disorder and are studying the functions and interactions of these proteins using both in vivo and in vitro methods. We are also developing methods for characterising mitochondrial oxidative stress in order to evaluate its significance in retinal degenerative disorders.

 

Quantitative Trait Locus (QTL) Identification In Isolate Populations

Summary and Purpose

The aims of the study are (i) to genetically map and identify quantitative trait loci (QTL) concerned with common human disorders in isolate populations; (ii) to characterise the genetic architecture of complex traits. We are studying Croatian island populations in collaboration with Croatian scientists and are also closely involved in a parallel study in the Orkney Islands, run by colleagues in the Department of Public Health Sciences, University of Edinburgh. We have measured over 300 different quantitative traits on each participant and performed high density genome-wide scans in each population.

 

Recent Publications

  • Dinour D, Gray NK, Ganon L, Knox AJ, Shalev H, Sela BA, Campbell S, Sawyer L, Shu X, Valsamidou E, Landau D, Wright AF, Holtzman EJ: Two novel homozygous SLC2A9 mutations cause renal hypouricemia type 2. Nephrol Dial Transplant 27:1035-1041, 2012.
    PubMed Abstract
  • Stolk L, Perry JR, Chasman DI, He C, Mangino M, Sulem P, Barbalic M, Broer L, Hayward C,........... Heath AC.... Wilson JF, Wolffenbuttel BH, Wright AF, ......, Visser JA, Lunetta KL: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat Genet 44:260-268, 2012.
    PubMed Abstract
  • Zoldos V, Horvat T, Novokmet M, Cuenin C, Muzinic A, Pucic M, Huffman JE, Gornik O, Polasek O, Campbell H, Hayward C, Wright AF, Rudan I, Owen K, McCarthy MI, Herceg Z, Lauc G: Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome
    Epigenetics 7:164-172, 2012.
    PubMed Abstract
  • Saldova R, Huffman JE, Adamczyk B, Muzinic A, Kattla JJ, Pucic M, Novokmet M, Abrahams JL, Hayward C, Rudan I, Wild SH, Wright AF, Polasek O, Lauc G, Campbell H, Wilson JF, Rudd PM: Association of medication with the human plasma N-glycome
    J Proteome Res 11:1821-1831, 2012.
    PubMed Abstract
  • Demirkan A, van Duijn CM, Ugocsai P, Isaacs A, Pramstaller PP, Liebisch G, Wilson JF, Johansson A, Rudan I, Aulchenko YS, .......... Huffman J, Hastie ND, Uitterlinden A, Franke L, Franklin CS, Vitart V, Nelson CP, Preuss M, Bis JC, O'Donnell CJ, Franceschini N, Witteman JC, Axenovich T, Oostra BA, Meitinger T, Hicks AA, Hayward C, Wright AF, Gyllensten U, Campbell H, Schmitz G: Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations
    PLoS Genet 8:e1002490, 2012.
    PubMed Abstract
  • Cipriani V, Matharu BK, Khan JC, Shahid H, Stanton CM, Hayward C, Wright AF, Bunce C, Clayton DG, Moore AT, Yates JR: Genetic variation in complement regulators and susceptibility to age-related macular degeneration
    Immunobiology 217:158-161, 2012.
    PubMed Abstract
  • Mitry D, Singh J, Yorston D, Siddiqui MA, Murphy AL, Wright AF, Fleck BW, Campbell H, Charteris DG: The fellow eye in retinal detachment: findings from the Scottish Retinal Detachment Study. Br J Ophthalmol 96:110-113, 2012.PubMed Abstract
  • Gakovic M, Shu X, Kasioulis I, Carpanini S, Moraga I, Wright AF: The role of RPGR in cilia formation and actin stability
    Hum Mol Genet 20:4840-4850, 2011.PubMed Abstract
  • Wain LV, Verwoert GC, O'Reilly PF, Shi G, Johnson T, Johnson AD, Bochud M, Rice KM, Henneman P, Smith AV, Ehret GB, Amin N, Larson MG, Mooser V, AU, Webster RJ, Zhang F, Peden JF, Schmidt H, Tanaka T, Campbell H, Igl W, Milaneschi Y, Hottenga JJ, Vitart V, et al : Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nat Genet 43:1005-1011, 2011. PubMed Abstract
  • Carrasquillo, M.M.; Belbin, O.; Zou, F.; Allen, M.; Ertekin-Taner, N.; Ansari, M.; Wilcox, S.L.; Kashino, M.R.; Ma, L.; Younkin, L.H.; Younkin, S.G.; Younkin, C.S.; Dincman, T.A.; Howard, M.E.; Howell, C.C.; Stanton, C.M.; Watson, C.M.; Crump, M.; Vitart, V.; Hayward, C.; Hastie, N.D.; Rudan, I.; Campbell, H.; Polasek, O.; Brown, K.; Passmore, P.; Craig, D.; McGuinness, B.; Todd, S.; Kehoe, P.G.; Mann, D.M.; Smith, A.D.; Beaumont, H.; Warden, D.; Holmes, C.; Heun, R.; Kolsch, H.; Kalsheker, N.; Pankratz, V.S.; Dickson, D.W.; Graff-Radford, N.R.; Petersen, R.C.; Wright, A.F.; Younkin, S.G. and Morgan, K. Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Abeta, and Alzheimer's disease. PLoS One. 5(1):e8764, 2010
    PubMed Abstract
  • Dinour D.; Gray, N.K.; Campbell, S.; Shu, X.; Sawyer, L.; Richardson, W.; Rechavi, G.; Amariglio, N.; Ganon, L.; Sela, B.A.; Bahat, H.; Goldman, M.; Weissgarten, J.; Millar, M.R.; Wright, A.F. and Holtzman, E.J. Homozygous SLC2A9 mutations cause severe renal hypouricemia. J Am Soc Nephrol. 21(1):64-72, 2010
    PubMed Abstract
  • Dupuis, J.; Langenberg, C.; ....Navarro, P.; .........Hayward, C.; ......... Vitart, V.; ......Wright, A.F...........and Barroso, I. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat.Genet. 42(2):105-116, 2010
    PubMed Absract
  • Igl, W.; Johansson, A.; Wilson, J.F.; Wild, S.H.; Polasek, O.; Hayward, C.; Vitart, V.; Hastie, N.; Rudan, P.; Gnewuch, C.; Schmitz, G.; Meitinger, T.; Pramstaller, P.P.; Hicks, A.A.; Oostra, B.A.; van Duijn, C.M.; Rudan, I.; Wright, A.; Campbell, H. and Gyllensten, U. Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. PLoS Genet. 6(1):e1000798, 2010
    PubMed Abstract
  • Johansson, A.; Marroni, F.; Hayward, C.; Franklin, C.S.; Kirichenko, A.V.; Jonasson, I.; Hicks, A.A.; Vitart, V.; Isaacs, A.; Axenovich, T.; Campbell, S.; Floyd, J.; Hastie, N.; Knott, S.; Lauc, G.; Pichler, I.; Rotim, K.; Wild, S.H.; Zorkoltseva, I.V.; Wilson, J.F.; Rudan, I.; Campbell, H.; Pattaro, C.; Pramstaller, P.; Oostra, B.A.; Wright, A.F.; van Duijn, C.M.; Aulchenko, Y.S. and Gyllensten, U. Linkage and Genome-wide Association Analysis of Obesity-related Phenotypes: Association of Weight With the MGAT1 Gene. Obesity 18(4):803-8, 2010
    PubMed Abstract
  • Liu, J.Z.; Tozzi, F.; Waterworth, D.M.; Pillai, S.G.; Muglia, P.; Middleton, L.; Berrettini, W.; Knouff, C.W.; Yuan, X.; Waeber, G.; Vollenweider, P.; Preisig, M.; Wareham, N.J.; Zhao, J.H.; Loos, R.J.; Barroso, I.; Khaw, K.T.; Grundy, S.; Barter, P.; Mahley, R.; Kesaniemi, A.; McPherson, R.; Vincent, J.B.; Strauss, J.; Kennedy, J.L.; Farmer, A.; McGuffin, P.; Day, R.; Matthews, K.; Bakke, P.; Gulsvik, A.; Lucae, S.; Ising, M.; Brueckl, T.; Horstmann, S.; Wichmann, H.E.; Rawal, R.; Dahmen, N.; Lamina, C.; Polasek, O.; Zgaga, L.; Huffman, J.; Campbell, S.; Kooner, J.; Chambers, J.C.; Burnett, M.S.; Devaney, J.M.; Pichard, A.D.; Kent, K.M.; Satler, L.; Lindsay, J.M.; Waksman, R.; Epstein, S.; Wilson, J.F.; Wild, S.H.; Campbell, H.; Vitart, V.; Reilly, M.P.; Li, M.; Qu, L.; Wilensky, R.; Matthai, W.; Hakonarson, H.H.; Rader, D.J.; Franke, A.; Wittig, M.; Schafer, A.; Uda, M.; Terracciano, A.; Xiao, X.; Busonero, F.; Scheet, P.; Schlessinger, D.; St Clair, D.; Rujescu, D.; Abecasis, G.R.; Grabe, H.J.; Teumer, A.; Volzke, H.; Petersmann, A.; John, U.; Rudan, I.; Hayward, C.; Wright, A.F.; Kolcic, I.; Wright, B.J.; Thompson, J.R.; Balmforth, A.J.; Hall, A.S.; Samani, N.J.; Anderson, C.A.; Ahmad, T.; Mathew, C.G.; Parkes, M.; Satsangi, J.; Caulfield, M.; Munroe, P.B.; Farrall, M.; Dominiczak, A.; Worthington, J.; Thomson, W.; Eyre, S.; Barton, A.; Mooser, V.; Francks, C. and Marchini, J. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat.Genet. 42(5):436-440, 2010
    PubMed Abstract
  • Navarro, P.; Vitart, V.; Hayward, C.; Tenesa, A.; Zgaga, L.; Juricic, D.; Polasek, O.; Hastie, N.D.; Rudan, I.; Campbell, H.; Wright, A.F.; Haley, C.S. and Knott, S.A. Genetic comparison of a Croatian isolate and CEPH European founders. Genet.Epidemiol 34(2):140-5, 2010
    PubMed Abstract
  • Repapi, E.; Sayers, I.; Wain, L.V.; Burton, P.R.; Johnson, T.; Obeidat, M.; Zhao, J.H.; Ramasamy, A.; Zhai, G.; Vitart, V.; Huffman, J.E.; Igl, W.; Albrecht, E.; Deloukas, P.; Henderson, J.; Granell, R.; McArdle, W.L.; Rudnicka, A.R.; Barroso, I.; Loos, R.J.; Wareham, N.J.; Mustelin, L.; Rantanen, T.; Surakka, I.; Imboden, M.; Wichmann, H.E.; Grkovic, I.; Jankovic, S.; Zgaga, L.; Hartikainen, A.L.; Peltonen, L.; Gyllensten, U.; Johansson, A.; Zaboli, G.; Campbell, H.; Wild, S.H.; Wilson, J.F.; Glaser, S.; Homuth, G.; Volzke, H.; Mangino, M.; Soranzo, N.; Spector, T.D.; Polasek, O.; Rudan, I.; Wright, A.F.; Heliovaara, M.; Ripatti, S.; Pouta, A.; Naluai, A.T.; Olin, A.C.; Toren, K.; Cooper, M.N.; James, A.L.; Palmer, L.J.; Hingorani, A.D.; Wannamethee, S.G.; Whincup, P.H.; Smith, G.D.; Ebrahim, S.; McKeever, T.M.; Pavord, I.D.; MacLeod, A.K.; Morris, A.D.; Porteous, D.J.; Cooper, C.; Dennison, E.; Shaheen, S.; Karrasch, S.; Schnabel, E.; Schulz, H.; Grallert, H.; Bouatia-Naji, N.; Delplanque, J.; Froguel, P.; Blakey, J.D.; Britton, J.R.; Morris, R.W.; Holloway, J.W.; Lawlor, D.A.; Hui, J.; Nyberg, F.; Jarvelin, M.R.; Jackson, C.; Kahonen, M.; Kaprio, J.; Probst-Hensch, N.M.; Koch, B.; Hayward, C.; Evans, D.M.; Elliott, P.; Strachan, D.P.; Hall, I.P. and Tobin, M.D. Genome-wide association study identifies five loci associated with lung function.
    Nat.Genet.     42(1):36-44, 2010
    PubMed Abstract

  • Key/Selected Publications
  • Rudan, I.; Carothers, A.D.; Polasek, O.; Hayward, C.; Vitart, V.; Biloglav, Z.; Kolcic, I.; Zgaga, L.; Ivankovic, D.; Vorko-Jovic, A.; Wilson, J.F.; Weber, J.L.; Hastie, N.; Wright, A. and Campbell, H. Quantifying the increase in average human heterozygosity due to urbanisation.
    Eur J Hum Genet 16(9):1097-102, 2008
    PubMed Abstract
  • Schoemaker, M.J.; Swerdlow, A.J.; Higgins, C.D.; Wright, A.F. and Jacobs, P.A. Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol 9(3):239-246, 2008
    PubMed Abstract
  • Vitart, V.; Rudan, I.; Hayward, C.; Gray, N.K.; Floyd, J.; Palmer, C.N.; Knott, S.A.; Kolcic, I.; Polasek, O.; Graessler, J.; Wilson, J.F.; Marinaki, A.; Riches, P.L.; Shu, X.; Janicijevic, B.; Smolej-Narancic, N.; Gorgoni, B.; Morgan, J.; Campbell, S.; Biloglav, Z.; Barac-Lauc, L.; Pericic, M.; Klaric, I.M.; Zgaga, L.; Skaric-Juric, T.; Wild, S.H.; Richardson, W.A.; Hohenstein, P.; Kimber, C.H.; Tenesa, A.; Donnelly, L.A.; Fairbanks, L.D.; Aringer, M.; McKeigue, P.M.; Ralston, S.H.; Morris, A.D.; Rudan, P.; Hastie, N.D.; Campbell, H. and Wright, A.F. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.
    Nat Genet 40(4):437-442, 2008
    PubMed Abstract
  • Campbell, H.; Carothers, A.D.; Rudan, I.; Hayward, C.; Biloglav, Z.; Barac, L.; Pericic, M.; Janicijevic, B.; Smolej-Narancic, N.; Polasek, O.; Kolcic, I.; Weber, J.L.; Hastie, N.D.; Rudan, P. and Wright, A.F. Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits. Hum Mol Genet 16(2):233-241, 2007
    PubMed Abstract
  • Shu, X.; Black, G.C.; Rice, J.M.; Hart-Holden, N.; Jones, A.; O'Grady, A.; Ramsden, S. and Wright, A.F. RPGR mutation analysis and disease: an update. Hum Mutat 28(4):322-328, 2007
    PubMed Abstract
  • Wright, A.F. and Shu, X. Focus on Molecules: RPGR. Experimental Eye Research 85(1):1-2, 2007 PubMed Abstract
  • Yates, J.R.; Sepp, T.; Matharu, B.K.; Khan, J.C.; Thurlby, D.A.; Shahid, H.; Clayton, D.G.; Hayward, C.; Morgan, J.; Wright, A.F.; Armbrecht, A.M.; Dhillon, B.; Deary, I.J.; Redmond, E.; Bird, A.C. and Moore, A.T. Complement C3 variant and the risk of age-related macular degeneration. New England Journal of Medicine 357(6):553-561, 2007
    PubMed Abstract
  • Rudan, I.; Campbell, H.; Carothers, A.D.; Hastie, N.D. and Wright, A.F. Contribution of consanguinuity to polygenic and multifactorial diseases. Nat Genet 38(11):1224-1225, 2006 PubMed Abstract
  • Vitart, V.; Biloglav, Z.; Hayward, C.; Janicijevic, B.; Smolej-Narancic, N.; Barac, L.; Pericic, M.; Klaric, I.M.; Skaric-Juric, T.; Barbalic, M.; Polasek, O.; Kolcic, I.; Carothers, A.; Rudan, P.; Hastie, N.; Wright, A.; Campbell, H. and Rudan, I. 3000 years of solitude: extreme differentiation in the island isolates of Dalmatia, Croatia. Eur J Hum Genet 14(4):478-487, 2006
    PubMed Abstract
  • Vitart, V.; Carothers, A.D.; Hayward, C.; Teague, P.; Hastie, N.D.; Campbell, H. and Wright, A.F. Increased level of linkage disequilibrium in rural compared with urban communities: a factor to consider in association-study design. Am J Hum Genet 76(5):763-772, 2005
    PubMed Abstract
  • Wright, A.F.; Jacobson, S.G.; Cideciyan, A.V.; Roman, A.J.; Shu, X.; Vlachantoni, D.; McInnes, R.R. and Riemersma, R.A. Life span and mitchondrial control of neurodegeneration.
    Nature Genetics     36(11):1153-1158, 2004
    PubMed Abstract
  • Wright, A.; Charlesworth, B.; Rudan, I.; Carothers, A. and Campbell, H. A polygenic basis for late-onset disease. Trends in Genetics 19(2):97-106, 2003
    PubMed Abstract
  • Boylan, J.P. and Wright, A.F. Identification of a novel protein interacting with RPGR.
    Human Molecular Genetics 9(14):2085-2093, 2000
    PubMed Abstract
  • Vervoort, R.; Lennon, A.; Bird, A.C.; Tulloch, B.; Axton, R.; Miano, M.G.; Meindl, A.; Meitinger, T.; Ciccodicola, A.A. and Wright, A.F. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nat Genet 25(4):462-466, 2000
    PubMed Abstract