Skip Navigation


Human Molecular Genetics Advance Access originally published online on December 5, 2007
Human Molecular Genetics 2008 17(5):768-774; doi:10.1093/hmg/ddm361
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
17/5/768    most recent
ddm361v3
ddm361v2
ddm361v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (26)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Cronin, S.
Right arrow Articles by Hardiman, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cronin, S.
Right arrow Articles by Hardiman, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A genome-wide association study of sporadic ALS in a homogenous Irish population

Simon Cronin1,2,*, Stephen Berger3, Jinhui Ding4, Jennifer C Schymick3,7, Nicole Washecka3, Dena G. Hernandez3, Matthew J. Greenway2, Daniel G. Bradley9, Bryan J. Traynor3,5,6,8 and Orla Hardiman2,10

1 Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland 2 Department of Neurology, Beaumont Hospital, Dublin 9, Ireland 3 Laboratory of Neurogenetics, National Institute on Aging 4 Computational Biology Core, Laboratory of Neurogenetics, National Molecular Genetics Unit 5 Neurogenetics Branch, National Institute of Neurological Disorders and Stroke and and 6 Molecular Genetics Unit, National Institutes of Health, Bethesda, MD, USA 7 Department of Physiology, Anatomy and Genetics, University of Oxford, Henry Wellcome Building of Gene Function, Oxford, UK 8 Neurology Department, Johns Hopkins University, Baltimore, MD, USA 9 Smurfit Institute of Genetics and 10 Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland

* To whom correspondence should be addressed at: The Irish ALS Research Group, Department of Neurology, Beaumont Hospital, Dublin 9, Ireland. Tel: +353 18092174; Fax: +353 18092302; Email: scronin{at}rcsi.ie

Received November 10, 2007; Accepted December 4, 2007

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive limb or bulbar weakness. Efforts to elucidate the disease-associated loci have to date produced conflicting results. One strategy to improve power in genome-wide studies is to genotype a genetically homogenous population. Such a population exhibits extended linkage disequilibrium (LD) and lower allelic heterogeneity to facilitate disease gene mapping. We sought to identify associated variants for ALS in the Irish, a stable population of relatively homogenous genetic background, and to replicate these findings in larger genetically out-bred populations. We conducted a genome-wide association study in 432 Irish individuals using Illumina HumanHap 550K single nucleotide polymorphism chips. We demonstrated extended LD and increased homogeneity in the Irish sample when compared to an out-bred population of mixed European ancestry. The Irish scan identified 35 loci associated with P-values below 0.0001. For replication, we identified seven chromosomal regions commonly associated in a joint analysis of genome-wide data on 958 ALS cases and 932 controls from Ireland and the previously published datasets from the US and The Netherlands. When pooled, the strongest association was a variant in the gene encoding DPP6, a component of type A neuronal transmembrane potassium channels. Further confirmation of the candidate loci is warranted in additional genome-wide datasets. We have made our individual genotyping data publicly available, contributing to a powerful world-wide resource to refine our understanding of the genetics of sporadic ALS.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
M. Sabatelli, F. Eusebi, A. Al-Chalabi, A. Conte, F. Madia, M. Luigetti, I. Mancuso, C. Limatola, F. Trettel, F. Sobrero, et al.
Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis
Hum. Mol. Genet., October 15, 2009; 18(20): 3997 - 4006.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. -M. Wills, S. Cronin, A. Slowik, D. Kasperaviciute, M. A. Van Es, J. M. Morahan, P. N. Valdmanis, V. Meininger, J. Melki, C. E. Shaw, et al.
A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS
Neurology, July 7, 2009; 73(1): 16 - 24.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. E. Landers, J. Melki, V. Meininger, J. D. Glass, L. H. van den Berg, M. A. van Es, P. C. Sapp, P. W. J. van Vught, D. M. McKenna-Yasek, H. M. Blauw, et al.
Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis
PNAS, June 2, 2009; 106(22): 9004 - 9009.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
T. Zaldivar, J. Gutierrez, G. Lara, M. Carbonara, G. Logroscino, and O. Hardiman
Reduced frequency of ALS in an ethnically mixed population: A population-based mortality study
Neurology, May 12, 2009; 72(19): 1640 - 1645.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
B. P. McEvoy, G. W. Montgomery, A. F. McRae, S. Ripatti, M. Perola, T. D. Spector, L. Cherkas, K. R. Ahmadi, D. Boomsma, G. Willemsen, et al.
Geographical structure and differential natural selection among North European populations
Genome Res., May 1, 2009; 19(5): 804 - 814.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Chio, J. C. Schymick, G. Restagno, S. W. Scholz, F. Lombardo, S.-L. Lai, G. Mora, H.-C. Fung, A. Britton, S. Arepalli, et al.
A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis
Hum. Mol. Genet., April 15, 2009; 18(8): 1524 - 1532.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. A. van Es, P.W.J. van Vught, G. van Kempen, H. M. Blauw, J. H. Veldink, and L. H. van den Berg
DPP6 IS ASSOCIATED WITH SUSCEPTIBILITY TO PROGRESSIVE SPINAL MUSCULAR ATROPHY
Neurology, March 31, 2009; 72(13): 1184 - 1185.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Awano, G. S. Johnson, C. M. Wade, M. L. Katz, G. C. Johnson, J. F. Taylor, M. Perloski, T. Biagi, I. Baranowska, S. Long, et al.
Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis
PNAS, February 24, 2009; 106(8): 2794 - 2799.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Cronin, H. M. Blauw, J. H. Veldink, M. A. van Es, R. A. Ophoff, D. G. Bradley, L. H. van den Berg, and O. Hardiman
Analysis of genome-wide copy number variation in Irish and Dutch ALS populations
Hum. Mol. Genet., November 1, 2008; 17(21): 3392 - 3398.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
R D. Bo, S Ghezzi, S Corti, D Santoro, A Prelle, M Mancuso, G Siciliano, C Briani, L Murri, N Bresolin, et al.
DPP6 gene variability confers increased risk of developing sporadic amyotrophic lateral sclerosis in Italian patients
J. Neurol. Neurosurg. Psychiatry, September 1, 2008; 79(9): 1085 - 1085.
[Full Text] [PDF]

Home page
 Clin. Chem.Home page
S. F. A. Grant and H. Hakonarson
Microarray Technology and Applications in the Arena of Genome-Wide Association
Clin. Chem., July 1, 2008; 54(7): 1116 - 1124.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.