Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis

Journal of Medical Genetics

Volumn 50, Issue 1, 2013, Pages 25-33

  Alcina, Antonio ^a   Fedetz, Maria ^a   Fernández, Óscar ^b   Saiz, Albert ^c   Izquierdo, Guillermo ^d   Lucas, Miguel ^d   Leyva, Laura ^b   García León, Juan Antonio ^b   Abad Grau, María del Mar ^e   Alloza, Iraide ^f   Antigüedad, Alfredo ^g   Garcia Barcina, María J ^g   Vandenbroeck, Koen ^f,h   Varadé, Jezabel ⁱ   de la Hera, Belén ⁱ   Arroyo, Rafael ^j   Comabella, Manuel ^k   Montalban, Xavier ^k   Petit Marty, Natalia ^l   Navarro, Arcadi ^l,m,n   Otaegui, David ^o   Olascoaga, Javier ^p   Blanco, Yolanda ^c   Urcelay, Elena ⁱ   Matesanz, Fuencisla ^a,d   more..

^a INSTITUTO DE PARASITOLOGÍA Y BIOMEDICINA LÓPEZ NEYRA   (Spain)

^b HOSPITAL REGIONAL UNIVERSITARIO DE MÁLAGA   (Spain)

^c HOSPITAL CLÍNIC   (Spain)

^d HOSPITAL UNIVERSITARIO VIRGEN MACARENA   (Spain)

^e UNIVERSITY OF GRANADA   (Spain)

^f UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^g HOSPITAL DE BASURTO   (Spain)

^h BASQUE FOUNDATION FOR SCIENCE   (Spain)

ⁱ INSTITUTO DE INVESTIGACIÓN SANITARIA DEL HOSPITAL CLÍNICO SAN CARLOS IDISSC   (Spain)

^j HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^k HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^l INSTITUTE OF EVOLUTIONARY BIOLOGY CSIC UNIVERSITAT POMPEU FABRA   (Spain)

^m UNIVERSITAT POMPEU FABRA   (Spain)

ⁿ INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^o BIODONOSTIA HEALTH RESEARCH INSTITUTE   (Spain)

^p HOSPITAL DONOSTIA   (Spain)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN BINDING PROTEIN; AVIL PROTEIN; CYTOCHROME P450; CYTOCHROME P450 27B1; ELONGATION FACTOR TU; FAM119B PROTEIN; KIF5A PROTEIN; LUCIFERASE; METTL1 PROTEIN; NUCLEAR PROTEIN; TETRASPANIN; TSFM PROTEIN; TSPAN31 PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ARTICLE; CAUCASIAN; CHROMATIN STRUCTURE; CONTROLLED STUDY; DIAGNOSTIC TEST ACCURACY STUDY; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FREQUENCY; GENE IDENTIFICATION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE MAPPING; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; MAJOR CLINICAL STUDY; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; PROMOTER REGION; QUANTITATIVE TRAIT LOCUS; REPORTER GENE; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM;

25-HYDROXYVITAMIN D3 1-ALPHA-HYDROXYLASE; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 12; ENHANCER ELEMENTS, GENETIC; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; KINESIN; METHYLTRANSFERASES; MULTIPLE SCLEROSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; TRANSCRIPTION, GENETIC;

EID: 84872140226     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2012-101085     Document Type: Article

References (42)

1. Hauser SL, Oksenberg JR. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2009;52:61-76.
2. McElroy JP, Oksenberg JR. Multiple sclerosis genetics. Curr Top Microbiol Immunol 2008;318:45-72.
3. Ramagopalan SV, Knight JC, Ebers GC. Multiple sclerosis and the major histocompatibility complex. Curr Opin Neurol 2009;22:219-25.
4. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM. Finding the missing heritability of complex diseases. Nature 2009;461:747-53.
5. Bomprezzi R, Kovanen PE, Martin R. New approaches to investigating heterogeneity in complex traits. J Med Genet 2003;40:553-9.
6. Fierabracci A, Milillo A, Locatelli F, Fruci D. The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: insights from genomic-wide association studies. Autoimmun Rev. Published Online First: May 2012. doi:10.1016/j.autrev. 2012.04.007.
7. Corrado L, Bergamaschi L, Barizzone N, Fasano ME, Guerini FR, Salvetti M, Galimberti D, Benedetti MD, Leone M, D'Alfonso S. Association of the CBLB gene with multiple sclerosis: new evidence from a replication study in an Italian population. J Med Genet 2011;48:210-11.
8. International Multiple Sclerosis Genetics Consortium; Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D'alfonso S, Blackburn H, Martinelli Boneschi F, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, D'hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppä V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Rückert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sørensen PS, Søndergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvänen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214-19.
9. Matesanz F, González-Pérez A, Lucas M, Sanna S, Gayán J, Urcelay E, Zara I, Pitzalis M, Cavanillas ML, Arroyo R, Zoledziewska M, Marrosu M, Fernández O, Leyva L, Alcina A, Fedetz M, Moreno-Rey C, Velasco J, Real LM, Ruiz-Peña JL, Cucca F, Ruiz A, Izquierdo G. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1. PLoS One 2012;7:e36140.
10. Kristjansdottir G, Sandling JK, Bonetti A, Roos IM, Milani L, Wang C, Gustafsdottir SM, Sigurdsson S, Lundmark A, Tienari PJ, Koivisto K, Elovaara I, Pirttilä T, Reunanen M, Peltonen L, Saarela J, Hillert J, Olsson T, Landegren U, Alcina A, Fernández O, Leyva L, Guerrero M, Lucas M, Izquierdo G, Matesanz F, Syvänen AC. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations. J Med Genet 2008;45:362-9.
11. Goris A, Boonen S, D'hooghe MB, Dubois B. Replication of KIF21B as a susceptibility locus for multiple sclerosis. J Med Genet 2010;47:775-6.
12. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet 2009;41:824-8.
13. Raychaudhuri S, Remmers EF, Lee AT, Hackett R, Guiducci C, Burtt NP, Gianniny L, Korman BD, Padyukov L, Kurreeman FA, Chang M, Catanese JJ, Ding B, Wong S, van der Helm-van Mil AH, Neale BM, Coblyn J, Cui J, Tak PP, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Criswell LA, Amos CI, Seldin MF, Kastner DL, Ardlie KG, Alfredsson L, Costenbader KH, Altshuler D, Huizinga TW, Shadick NA, Weinblatt ME, de Vries N, Worthington J, Seielstad M, Toes RE, Karlson EW, Begovich AB, Klareskog L, Gregersen PK, Daly MJ, Plenge RM. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet 2008;40:1216-23.
14. Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, Westra HJ, Fehrmann RS, Kurreeman FA, Thomson B, Gupta N, Romanos J, McManus R, Ryan AW, Turner G, Brouwer E, Posthumus MD, Remmers EF, Tucci F, Toes R, Grandone E, Mazzilli MC, Rybak A, Cukrowska B, Coenen MJ, Radstake TR, van Riel PL, Li Y, de Bakker PI, Gregersen PK, Worthington J, Siminovitch KA, Klareskog L, Huizinga TW, Wijmenga C, Plenge RM. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet 2011;7:e1002.
15. Alcina A, Vandenbroeck K, Otaegui D, Saiz A, Gonzalez JR, Fernandez O, Cavanillas ML, Cénit MC, Arroyo R, Alloza I, García-Barcina M, Antigüedad A, Leyva L, Izquierdo G, Lucas M, Fedetz M, Pinto-Medel MJ, Olascoaga J, Blanco Y, Comabella M, Montalban X, Urcelay E, Matesanz F. The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis. Genes Immun 2010;11:439-45.
16. Fung EY, Smyth DJ, Howson JM, Cooper JD, Walker NM, Stevens H, Wicker LS, Todd JA. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun 2009;10:188-91.
17. Ramagopalan SV, Dyment DA, Cader MZ, Morrison KM, Disanto G, Morahan JM, Berlanga-Taylor AJ, Handel A, De Luca GC, Sadovnick AD, Lepage P, Montpetit A, Ebers GC. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 2011;70:881-6.
18. Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, Hyppönen E, Dunger DB, Ramos-Lopez E, Badenhoop K, Nejentsev S, Todd JA. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes 2007;56:2616-21.
19. Sundqvist E, Bäärnhielm M, Alfredsson L, Hillert J, Olsson T, Kockum I. Confirmation of association between multiple sclerosis and CYP27B1. Eur J Hum Genet 2010;18:1349-52.
20. Gandhi KS, McKay FC, Cox M, Riveros C, Armstrong N, Heard RN, Vucic S, Williams DW, Stankovich J, Brown M, Danoy P, Stewart GJ, Broadley S, Moscato P, Lechner-Scott J, Scott RJ, Booth DR ANZgene Multiple Sclerosis Genetics Consortium. The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet 2010;19:2134-43.
21. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-31.
22. Cavanillas ML, Fernández O, Comabella M, Alcina A, Fedetz M, Izquierdo G, Lucas M, Cénit MC, Arroyo R, Vandenbroeck K, Alloza I, García-Barcina M, Antigüedad A, Leyva L, Gómez CL, Olascoaga J, Otaegui D, Blanco Y, Saiz A, Montalbán X, Matesanz F, Urcelay E. Replication of top markers of a genome-wide association study in multiple sclerosis in Spain. Genes Immun 2010;12:110-15.
23. Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005;76:887-93.
24. Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Statist Sic B 1995;57:289-300.
25. Sarkar SK. False discovery and false nondiscovery rates in single-step multiple testing procedures. Ann Stat 2006;34:394-415.
26. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005,21:263-5.
27. Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R, Maouche S, Germain M, Lackner K, Rossmann H, Eleftheriadis M, Sinning CR, Schnabel RB, Lubos E, Mennerich D, Rust W, Perret C, Proust C, Nicaud V, Loscalzo J, Hübner N, Tregouet D, Münzel T, Ziegler A, Tiret L, Blankenberg S, Cambien F. Genetics and beyond-the transcriptome of human monocytes and disease susceptibility. PLoS One 2010;5:e10693.
28. Dixon AL, Liang L, Moffatt MF, Chen W, Heath S, Wong KC, Taylor J, Burnett E, Gut I, Farrall M, Lathrop GM, Abecasis GR, Cookson WO. A genome-wide association study of global gene expression. Nat Genet 2007;39:1202-7.
29. Montgomery SB, Sammeth M, Gutierrez-Arcelus M, Lach RP, Ingle C, Nisbett J, Guigo R, Dermitzakis ET. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 2010;464:773-7.
30. Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beazley C, Ingle CE, Dunning M, Flicek P, Koller D, Montgomery S, Tavaré S, Deloukas P, Dermitzakis ET. Population genomics of human gene expression. Nat Genet 2007;39:1217-24.
31. Dimas AS, Deutsch S, Stranger BE, Montgomery SB, Borel C, Attar-Cohen H, Ingle C, Beazley C, Gutierrez Arcelus M, Sekowska M, Gagnebin M, Nisbett J, Deloukas P, Dermitzakis ET, Antonarakis SE. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 2009;325:1246-50.
32. Ceribelli M, Dolfini D, Merico D, Gatta R, Viganò AM, Pavesi G, Mantovani R. The histone-like NF-Y is a bifunctional transcription factor. Mol Cell Biol 2008;28:2047-58.
33. Sakabe NJ, Aneas I, Shen T, Shokri L, Park SY, Bulyk ML, Evans SM, Nobrega MA. Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function. Hum Mol Genet 2012;21:2194-204.
34. Zarnegar MA, Chen J, Rothenberg EV. Cell-type-specific activation and repression of PU.1 by a complex of discrete, functionally specialized cis-regulatory elements. Mol Cell Biol 2010;30:4922-39.
35. Pinskaya M, Morillon A. Histone H3 lysine 4 di-methylation: a novel mark for transcriptional fidelity? Epigenetics 2009;4:302-6.
36. Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, Sim HS, Peh SQ, Mulawadi FH, Ong CT, Orlov YL, Hong S, Zhang Z, Landt S, Raha D, Euskirchen G, Wei CL, Ge W, Wang H, Davis C, Fisher-Aylor KI, Mortazavi A, Gerstein M, Gingeras T, Wold B, Sun Y, Fullwood MJ, Cheung E, Liu E, Sung WK, Snyder M, Ruan Y. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 2012;148:84-98.
37. Chepelev I, Wei G, Wangsa D, Tang Q, Zhao K. Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization. Cell Res 2012;22:490-503.
38. Adams JS, Hewison M. Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 2012;523:95-102.
39. Simon KC, Munger KL, Kraft P, Hunter DJ, De Jager PL, Ascherio A. Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Neurol 2011;258:1676-82.
40. Orton SM, Morris AP, Herrera BM, Ramagopalan SV, Lincoln MR, Chao MJ, Vieth R, Sadovnick AD, Ebers GC. Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 2008;88:441-7.
41. Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, Herrmann E, Badenhoop K, Zeuzem S, Sarrazin C. Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy. J Hepatol 2011;54:887-93.
42. Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, Szegedi G, Brun JG, Gesztelyi R, Zeher M, Bodolay E. The complex role of vitamin D in autoimmune diseases. Scand J Immunol 2008;68:261-9.