Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis

被引：14

作者：

Sorosina, Melissa ^{[1
]}

Esposito, Federica ^{[1
,2
]}

Guaschino, Clara ^{[1
,2
]}

Clarelli, Ferdinando ^{[1
]}

Barizzone, Nadia

Osiceanu, Ana Maria ^{[1
]}

Brambilla, Paola ^{[1
]}

Mascia, Elisabetta ^{[1
]}

Cavalla, Paola

Gallo, Paolo

Martinelli, Vittorio ^{[2
]}

Leone, Maurizio ^{[3
]}

Comi, Giancarlo ^{[1
,2
]}

D'Alfonso, Sandra

Boneschi, Filippo Martinelli ^{[1
,2
]}

机构：

[1] Ist Sci San Raffaele, Inst Expt Neurol INSPE, Lab Genet Neurol Complex Disorders, Div Neurosci, I-20132 Milan, Italy

[2] Ist Sci San Raffaele, Inst Expt Neurol INSPE, Div Neurosci, Dept Neurol, I-20132 Milan, Italy

[3] Univ Piemonte Orientale, Interdisciplinary Res Ctr Autoimmune Dis, Novara, Italy

来源：

MULTIPLE SCLEROSIS JOURNAL | 2015年 / 21卷 / 11期

关键词：

Primary-progressive; relapsing-remitting; multiple sclerosis; age of onset; weighted genetic risk score; genetic risk;

D O I：

10.1177/1352458514561910

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) (n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= -0.1; p=5 x 10(-3)) and a later age at onset in PrMS cases (rho=0.07; p=0.15) (p of difference of regression=1.4 x 10(-2)). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.

引用

页码：1463 / 1467

页数：5

共 14 条

[1] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis [J].

Beecham, Ashley H. ;

Patsopoulos, Nikolaos A. ;

Xifara, Dionysia K. ;

Davis, Mary F. ;

Kemppinen, Anu ;

Cotsapas, Chris ;

Shah, Tejas S. ;

Spencer, Chris ;

Booth, David ;

Goris, An ;

Oturai, Annette ;

Saarela, Janna ;

Fontaine, Bertrand ;

Hemmer, Bernhard ;

Martin, Claes ;

Zipp, Frauke ;

D'Alfonso, Sandra ;

Martinelli-Boneschi, Filippo ;

Taylor, Bruce ;

Harbo, Hanne F. ;

Kockum, Ingrid ;

Hillert, Jan ;

Olsson, Tomas ;

Ban, Maria ;

Oksenberg, Jorge R. ;

Hintzen, Rogier ;

Barcellos, Lisa F. ;

Agliardi, Cristina ;

Alfredsson, Lars ;

Alizadeh, Mehdi ;

Anderson, Carl ;

Andrews, Robert ;

Sondergaard, Helle Bach ;

Baker, Amie ;

Band, Gavin ;

Baranzini, Sergio E. ;

Barizzone, Nadia ;

Barrett, Jeffrey ;

Bellenguez, Celine ;

Bergamaschi, Laura ;

Bernardinelli, Luisa ;

Berthele, Achim ;

Biberacher, Viola ;

Binder, Thomas M. C. ;

Blackburn, Hannah ;

Bomfim, Izaura L. ;

Brambilla, Paola ;

Broadley, Simon ;

Brochet, Bruno ;

Brundin, Lou .

NATURE GENETICS, 2013, 45 (11) :1353-+

[2] Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score [J].

De Jager, Philip L. ;

Chibnik, Lori B. ;

Cui, Jing ;

Reischl, Joachim ;

Lehr, Stephan ;

Simon, K. Claire ;

Aubin, Cristin ;

Bauer, David ;

Heubach, Juergen F. ;

Sandbrink, Rupert ;

Tyblova, Michaela ;

Lelkova, Petra ;

Havrdova, Eva ;

Pohl, Christoph ;

Horakova, Dana ;

Ascherio, Alberto ;

Hafler, David A. ;

Karlson, Elizabeth W. .

LANCET NEUROLOGY, 2009, 8 (12) :1111-1119

[3] Natural history of primary progressive multiple sclerosis [J].

Ebers, GC .

MULTIPLE SCLEROSIS JOURNAL, 2004, 10 :S8-S13

[4] Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis [J].

Harbo, Hanne F. ;

Isobe, Noriko ;

Berg-Hansen, Pal ;

Bos, Steffan D. ;

Caillier, Stacy J. ;

Gustavsen, Marte W. ;

Mero, Inger-Lise ;

Celius, Elisabeth Gulowsen ;

Hauser, Stephen L. ;

Oksenberg, Jorge R. ;

Gourraud, Pierre-Antoine .

MULTIPLE SCLEROSIS JOURNAL, 2014, 20 (06) :660-668

[5] Genotype-phenotype correlation for non-HLA disease associated risk alleles in multiple sclerosis [J].

Harding, Katharine ;

Ingram, Gillian ;

Cossburn, Mark ;

Hirst, Claire ;

Pickersgill, Trevor ;

Ben-Shlomo, Yoav ;

Robertson, Neil .

NEUROSCIENCE LETTERS, 2012, 526 (01) :15-19

[6] Genetic burden in multiple sclerosis families [J].

Isobe, N. ;

Damotte, V. ;

Lo Re, V. ;

Ban, M. ;

Pappas, D. ;

Guillot-Noel, L. ;

Rebeix, I. ;

Compston, A. ;

Mack, T. ;

Cozen, W. ;

Fontaine, B. ;

Hauser, S. L. ;

Oksenberg, J. R. ;

Sawcer, S. ;

Gourraud, P-A .

GENES AND IMMUNITY, 2013, 14 (07) :434-440

[7] Multiple Sclerosis Susceptibility-Associated SNPs Do Not Influence Disease Severity Measures in a Cohort of Australian MS Patients [J].

Jensen, Cathy J. ;

Stankovich, Jim ;

Van der Walt, Anneke ;

Bahlo, Melanie ;

Taylor, Bruce V. ;

van der Mei, Ingrid A. F. ;

Foote, Simon J. ;

Kilpatrick, Trevor J. ;

Johnson, Laura J. ;

Wilkins, Ella ;

Field, Judith ;

Danoy, Patrick ;

Brown, Matthew A. ;

Rubio, Justin P. ;

Butzkueven, Helmut .

PLOS ONE, 2010, 5 (03)

[8]

Masterman T, 2000, ANN NEUROL, V48, P211, DOI 10.1002/1531-8249(200008)48:2<211::AID-ANA11>3.3.CO

[9]

2-I

[10] The diagnosis and management of multiple sclerosis [J].

Poser, CM .

ACTA NEUROLOGICA SCANDINAVICA, 2005, 112 (03) :199-201

← 1 2 →