A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS
Identifieur interne : 000558 ( Ncbi/Checkpoint ); précédent : 000557; suivant : 000559A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS
Auteurs : 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 ; G A. Rouleau ; E M. C. Fisher ; P J. Shaw ; K E. Morrison ; R. Pamphlett ; L H. Van Den Berg ; D A. Figlewicz ; P M. Andersen ; A. Al-Chalabi ; O. Hardiman ; S. Purcell ; J E. Landers ; R H. BrownSource :
- Neurology [ 0028-3878 ] ; 2009.
Abstract
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.
We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425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.
The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI], 1.02–1.16,
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.
= amyotrophic lateral sclerosis;
= confidence interval;
= genome-wide association studies;
= odds ratio;
= sporadic ALS;
= single nucleotide polymorphism.
Url:
DOI: 10.1212/WNL.0b013e3181a18674
PubMed: 19321847
PubMed Central: 2707108
Affiliations:
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Morahan</name></author><author><name sortKey="Valdmanis, P N" sort="Valdmanis, P N" uniqKey="Valdmanis P" first="P N." last="Valdmanis">P N. Valdmanis</name></author><author><name sortKey="Meininger, V" sort="Meininger, V" uniqKey="Meininger V" first="V" last="Meininger">V. Meininger</name></author><author><name sortKey="Melki, J" sort="Melki, J" uniqKey="Melki J" first="J" last="Melki">J. Melki</name></author><author><name sortKey="Shaw, C E" sort="Shaw, C E" uniqKey="Shaw C" first="C E." last="Shaw">C E. Shaw</name></author><author><name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A." last="Rouleau">G A. Rouleau</name></author><author><name sortKey="Fisher, E M C" sort="Fisher, E M C" uniqKey="Fisher E" first="E M. C." last="Fisher">E M. C. Fisher</name></author><author><name sortKey="Shaw, P J" sort="Shaw, P J" uniqKey="Shaw P" first="P J." last="Shaw">P J. Shaw</name></author><author><name sortKey="Morrison, K E" sort="Morrison, K E" uniqKey="Morrison K" first="K E." last="Morrison">K E. Morrison</name></author><author><name sortKey="Pamphlett, R" sort="Pamphlett, R" uniqKey="Pamphlett R" first="R" last="Pamphlett">R. Pamphlett</name></author><author><name sortKey="Van Den Berg, L H" sort="Van Den Berg, L H" uniqKey="Van Den Berg L" first="L H." last="Van Den Berg">L H. Van Den Berg</name></author><author><name sortKey="Figlewicz, D A" sort="Figlewicz, D A" uniqKey="Figlewicz D" first="D A." last="Figlewicz">D A. Figlewicz</name></author><author><name sortKey="Andersen, P M" sort="Andersen, P M" uniqKey="Andersen P" first="P M." last="Andersen">P M. Andersen</name></author><author><name sortKey="Al Chalabi, A" sort="Al Chalabi, A" uniqKey="Al Chalabi A" first="A" last="Al-Chalabi">A. Al-Chalabi</name></author><author><name sortKey="Hardiman, O" sort="Hardiman, O" uniqKey="Hardiman O" first="O" last="Hardiman">O. Hardiman</name></author><author><name sortKey="Purcell, S" sort="Purcell, S" uniqKey="Purcell S" first="S" last="Purcell">S. Purcell</name></author><author><name sortKey="Landers, J E" sort="Landers, J E" uniqKey="Landers J" first="J E." last="Landers">J E. Landers</name></author><author><name sortKey="Brown, R H" sort="Brown, R H" uniqKey="Brown R" first="R H." last="Brown">R H. Brown</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19321847</idno><idno type="pmc">2707108</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707108</idno><idno type="RBID">PMC:2707108</idno><idno type="doi">10.1212/WNL.0b013e3181a18674</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001032</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001032</idno><idno type="wicri:Area/Pmc/Curation">000E93</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E93</idno><idno type="wicri:Area/Pmc/Checkpoint">002876</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002876</idno><idno type="wicri:Area/Ncbi/Merge">000558</idno><idno type="wicri:Area/Ncbi/Curation">000558</idno><idno type="wicri:Area/Ncbi/Checkpoint">000558</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS</title><author><name sortKey="Wills, A M" sort="Wills, A M" uniqKey="Wills A" first="A M." last="Wills">A M. Wills</name></author><author><name sortKey="Cronin, S" sort="Cronin, S" uniqKey="Cronin S" first="S" last="Cronin">S. Cronin</name></author><author><name sortKey="Slowik, A" sort="Slowik, A" uniqKey="Slowik A" first="A" last="Slowik">A. Slowik</name></author><author><name sortKey="Kasperaviciute, D" sort="Kasperaviciute, D" uniqKey="Kasperaviciute D" first="D" last="Kasperaviciute">D. Kasperaviciute</name></author><author><name sortKey="Van Es, M A" sort="Van Es, M A" uniqKey="Van Es M" first="M A." last="Van Es">M A. Van Es</name></author><author><name sortKey="Morahan, J M" sort="Morahan, J M" uniqKey="Morahan J" first="J M." last="Morahan">J M. Morahan</name></author><author><name sortKey="Valdmanis, P N" sort="Valdmanis, P N" uniqKey="Valdmanis P" first="P N." last="Valdmanis">P N. Valdmanis</name></author><author><name sortKey="Meininger, V" sort="Meininger, V" uniqKey="Meininger V" first="V" last="Meininger">V. Meininger</name></author><author><name sortKey="Melki, J" sort="Melki, J" uniqKey="Melki J" first="J" last="Melki">J. Melki</name></author><author><name sortKey="Shaw, C E" sort="Shaw, C E" uniqKey="Shaw C" first="C E." last="Shaw">C E. Shaw</name></author><author><name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A." last="Rouleau">G A. Rouleau</name></author><author><name sortKey="Fisher, E M C" sort="Fisher, E M C" uniqKey="Fisher E" first="E M. C." last="Fisher">E M. C. Fisher</name></author><author><name sortKey="Shaw, P J" sort="Shaw, P J" uniqKey="Shaw P" first="P J." last="Shaw">P J. Shaw</name></author><author><name sortKey="Morrison, K E" sort="Morrison, K E" uniqKey="Morrison K" first="K E." last="Morrison">K E. Morrison</name></author><author><name sortKey="Pamphlett, R" sort="Pamphlett, R" uniqKey="Pamphlett R" first="R" last="Pamphlett">R. Pamphlett</name></author><author><name sortKey="Van Den Berg, L H" sort="Van Den Berg, L H" uniqKey="Van Den Berg L" first="L H." last="Van Den Berg">L H. Van Den Berg</name></author><author><name sortKey="Figlewicz, D A" sort="Figlewicz, D A" uniqKey="Figlewicz D" first="D A." last="Figlewicz">D A. Figlewicz</name></author><author><name sortKey="Andersen, P M" sort="Andersen, P M" uniqKey="Andersen P" first="P M." last="Andersen">P M. Andersen</name></author><author><name sortKey="Al Chalabi, A" sort="Al Chalabi, A" uniqKey="Al Chalabi A" first="A" last="Al-Chalabi">A. Al-Chalabi</name></author><author><name sortKey="Hardiman, O" sort="Hardiman, O" uniqKey="Hardiman O" first="O" last="Hardiman">O. Hardiman</name></author><author><name sortKey="Purcell, S" sort="Purcell, S" uniqKey="Purcell S" first="S" last="Purcell">S. Purcell</name></author><author><name sortKey="Landers, J E" sort="Landers, J E" uniqKey="Landers J" first="J E." last="Landers">J E. Landers</name></author><author><name sortKey="Brown, R H" sort="Brown, R H" uniqKey="Brown R" first="R H." last="Brown">R H. Brown</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><idno type="eISSN">1526-632X</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>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.</p></sec><sec><title>Methods:</title><p>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.</p></sec><sec><title>Results:</title><p>The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI], 1.02–1.16, <italic>p</italic> = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07–1.45, <italic>p</italic> = 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86–1.10, <italic>p</italic> = 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92–1.27, <italic>p</italic> = 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, <italic>p</italic> = 0.22).</p></sec><sec><title>Conclusions:</title><p>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.</p></sec><sec><title>GLOSSARY</title><def-list list-type="abr"><def-item><term><bold>ALS</bold></term><def><p> = amyotrophic lateral sclerosis; </p></def></def-item><def-item><term><bold>CI</bold></term><def><p> = confidence interval; </p></def></def-item><def-item><term><bold>GWAS</bold></term><def><p> = genome-wide association studies; </p></def></def-item><def-item><term><bold>OR</bold></term><def><p> = odds ratio; </p></def></def-item><def-item><term><bold>SALS</bold></term><def><p> = sporadic ALS; </p></def></def-item><def-item><term><bold>SNP</bold></term><def><p> = single nucleotide polymorphism.</p></def></def-item></def-list></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Al Chalabi, A" sort="Al Chalabi, A" uniqKey="Al Chalabi A" first="A" last="Al-Chalabi">A. Al-Chalabi</name><name sortKey="Andersen, P M" sort="Andersen, P M" uniqKey="Andersen P" first="P M." last="Andersen">P M. Andersen</name><name sortKey="Brown, R H" sort="Brown, R H" uniqKey="Brown R" first="R H." last="Brown">R H. Brown</name><name sortKey="Cronin, S" sort="Cronin, S" uniqKey="Cronin S" first="S" last="Cronin">S. Cronin</name><name sortKey="Figlewicz, D A" sort="Figlewicz, D A" uniqKey="Figlewicz D" first="D A." last="Figlewicz">D A. Figlewicz</name><name sortKey="Fisher, E M C" sort="Fisher, E M C" uniqKey="Fisher E" first="E M. C." last="Fisher">E M. C. Fisher</name><name sortKey="Hardiman, O" sort="Hardiman, O" uniqKey="Hardiman O" first="O" last="Hardiman">O. Hardiman</name><name sortKey="Kasperaviciute, D" sort="Kasperaviciute, D" uniqKey="Kasperaviciute D" first="D" last="Kasperaviciute">D. Kasperaviciute</name><name sortKey="Landers, J E" sort="Landers, J E" uniqKey="Landers J" first="J E." last="Landers">J E. Landers</name><name sortKey="Meininger, V" sort="Meininger, V" uniqKey="Meininger V" first="V" last="Meininger">V. Meininger</name><name sortKey="Melki, J" sort="Melki, J" uniqKey="Melki J" first="J" last="Melki">J. Melki</name><name sortKey="Morahan, J M" sort="Morahan, J M" uniqKey="Morahan J" first="J M." last="Morahan">J M. Morahan</name><name sortKey="Morrison, K E" sort="Morrison, K E" uniqKey="Morrison K" first="K E." last="Morrison">K E. Morrison</name><name sortKey="Pamphlett, R" sort="Pamphlett, R" uniqKey="Pamphlett R" first="R" last="Pamphlett">R. Pamphlett</name><name sortKey="Purcell, S" sort="Purcell, S" uniqKey="Purcell S" first="S" last="Purcell">S. Purcell</name><name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A." last="Rouleau">G A. Rouleau</name><name sortKey="Shaw, C E" sort="Shaw, C E" uniqKey="Shaw C" first="C E." last="Shaw">C E. Shaw</name><name sortKey="Shaw, P J" sort="Shaw, P J" uniqKey="Shaw P" first="P J." last="Shaw">P J. Shaw</name><name sortKey="Slowik, A" sort="Slowik, A" uniqKey="Slowik A" first="A" last="Slowik">A. Slowik</name><name sortKey="Valdmanis, P N" sort="Valdmanis, P N" uniqKey="Valdmanis P" first="P N." last="Valdmanis">P N. Valdmanis</name><name sortKey="Van Den Berg, L H" sort="Van Den Berg, L H" uniqKey="Van Den Berg L" first="L H." last="Van Den Berg">L H. Van Den Berg</name><name sortKey="Van Es, M A" sort="Van Es, M A" uniqKey="Van Es M" first="M A." last="Van Es">M A. Van Es</name><name sortKey="Wills, A M" sort="Wills, A M" uniqKey="Wills A" first="A M." last="Wills">A M. Wills</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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