Change search
ReferencesLink to record
Permanent link

Direct link
A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS.
Show others and affiliations
2009 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 73, no 1, 16-24 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. METHODS: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls. RESULTS: The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI], 1.02-1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07-1.45, p = 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86-1.10, p = 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92-1.27, p = 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97-1.16, p = 0.22). CONCLUSIONS: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS.

Place, publisher, year, edition, pages
American Academy of Neurology , 2009. Vol. 73, no 1, 16-24 p.
National Category
URN: urn:nbn:se:umu:diva-35509DOI: 10.1212/WNL.0b013e3181a18674PubMedID: 19321847OAI: diva2:344767
Available from: 2010-08-20 Created: 2010-08-20 Last updated: 2010-12-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Andersen, Peter M
By organisation
In the same journal

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 18 hits
ReferencesLink to record
Permanent link

Direct link