Document Detail

Screening for replication of genome-wide SNP associations in sporadic ALS.
MedLine Citation:
PMID:  18987618     Owner:  NLM     Status:  MEDLINE    
We recently reported a joint analysis of genome-wide association (GWA) data on 958 sporadic amyotrophic lateral sclerosis (ALS) cases and 932 controls from Ireland and the publicly available data sets from the United States and the Netherlands. The strongest pooled association was rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene. Here, we sought confirmation of joint analysis signals in both an expanded Irish and a Polish ALS cohort. Among 287 522 autosomal single-nucleotide polymorphisms (SNPs), 27 were commonly associated on joint analysis of the Irish, US and Dutch GWAs. These 27 SNPs were genotyped in an expanded Irish cohort (312 patients with SALS; 259 controls) and an additional Polish cohort (218 patients; 356 controls). Eleven SNPs, including rs10260404, reached a final P-value below 0.05 in the Irish cohort. In the Polish cohort, only one SNP, rs6299711, showed nominal association with ALS. Pooling of data for 1267 patients with ALS and 1336 control subjects did not identify any association reaching Bonferroni significance (P<1.74 x 10(-7)). The present strategy did not reveal any consistently associated SNP across four populations. The result for DPP6 is surprising, as it has been replicated elsewhere. We discuss the possible interpretations and implications of these findings for future ALS GWA studies both within and between populations.
Simon Cronin; Barbara Tomik; Daniel G Bradley; Agnieszka Slowik; Orla Hardiman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-05
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  17     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-16     Completed Date:  2009-02-20     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  213-8     Citation Subset:  IM    
Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
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MeSH Terms
Amyotrophic Lateral Sclerosis / genetics*
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study*
Middle Aged
Nerve Tissue Proteins / genetics
Peptide Hydrolases / genetics
Polymorphism, Single Nucleotide*
Potassium Channels / genetics
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Potassium Channels; EC 3.4.-/DPP6 protein, human; EC 3.4.-/Peptide Hydrolases; EC 3.4.14.-/Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Comment In:
Eur J Hum Genet. 2009 Feb;17(2):137-8   [PMID:  18985074 ]

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