ABCA7罕见变异与阿尔茨海默病风险。

ABCA7 rare variants and Alzheimer disease risk.

作者信息

Le Guennec Kilan, Nicolas Gaël, Quenez Olivier, Charbonnier Camille, Wallon David, Bellenguez Céline, Grenier-Boley Benjamin, Rousseau Stéphane, Richard Anne-Claire, Rovelet-Lecrux Anne, Bacq Delphine, Garnier Jean-Guillaume, Olaso Robert, Boland Anne, Meyer Vincent, Deleuze Jean-François, Amouyel Philippe, Munter Hans Markus, Bourque Guillaume, Lathrop Mark, Frebourg Thierry, Redon Richard, Letenneur Luc, Dartigues Jean-François, Pasquier Florence, Rollin-Sillaire Adeline, Génin Emmanuelle, Lambert Jean-Charles, Hannequin Didier, Campion Dominique

机构信息

From INSERM (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.C.R., A.R.-L., T.F., D.H., D.C.), U1079, IRIB, University of Rouen, Normandy University; Normandy Centre for Genomic Medicine and Personalized Medicine (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.-C.R., A.R.-L., T.F., D.H., D.C.), Rouen; Department of Genetics (G.N., T.F., D.H.), CNR-MAJ (G.N., O.Q., C.C., D.W., S.R., A.-C.R., F.P., A.R.-S., D.H., D.C.), and Department of Neurology (D.W., D.H.), Rouen University Hospital; INSERM (C.B., B.G.-B., P.A., J.-C.L.), U1167, Lille; Institut Pasteur de Lille (C.B., B.G.-B., P.A., J.-C.L.); Université Lille-Nord de France (C.B., B.G.-B., P.A., J.-C.L.); Centre National de Génotypage (D.B., J.-G.G., R.O., A.B., V.M., J.-F.Deleuze.), Institut de Génomique, CEA, Evry; Fondation Jean Dausset (J.-F.Deleuze.), Centre d'Etudes du Polymorphisme Humain, Paris, France; McGill University and Génome Québec Innovation Centre (H.M.M., G.B., M.L.), Montréal, Canada; INSERM (R.R.), UMR 1087, l'Institut du Thorax, CHU Nantes; CNRS (R.R.), UMR 6291, Université de Nantes; INSERM (L.L., J.-F.Dartigues.), U897, Bordeaux; University of Bordeaux (L.L., J.-F.Dartigues.); Department of Neurology (F.P., A.R.S.), Lille University Hospital; INSERM (E.G.), UMR1078, CHU Brest, Université Bretagne Occidentale, Brest; and Department of Research (D.C.), Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.

出版信息

Neurology. 2016 Jun 7;86(23):2134-7. doi: 10.1212/WNL.0000000000002627. Epub 2016 Apr 1.

DOI:10.1212/WNL.0000000000002627

PMID:27037229

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4898320/

Abstract

OBJECTIVE

To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.

METHODS

We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.

RESULTS

After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 × 10(-7)).

CONCLUSIONS

These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.

摘要

目的

在病例对照研究中探讨ABCA7罕见编码变异与阿尔茨海默病（AD）之间的关联。

方法

我们对484例法国早发性AD患者和590例种族匹配的对照进行了全外显子组分析。

结果

在合并罕见变异（次要等位基因频率≤1%）后，我们在病例组中检测到ABCA7功能丧失（LOF）和预测的有害错义变异富集（优势比[OR] 3.40，95%置信区间[CI] 1.68 - 7.35，p = 0.0002）。对先前发表的数据进行荟萃分析后，我们发现在来自法国和比利时的1256例患者和1347例对照的合并样本中，OR为2.81（95% CI 1.89 - 4.20，p = 3.60×10⁻⁷）。

结论

这些结果证实ABCA7 LOF变异在AD患者中富集，并将这一发现扩展到预测的有害错义变异。

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Hum Mutat. 2015 Dec;36(12):1226-35. doi: 10.1002/humu.22908. Epub 2015 Oct 14.

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Mol Psychiatry. 2016 Jun;21(6):831-6. doi: 10.1038/mp.2015.121. Epub 2015 Aug 25.

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ABCA7罕见变异与阿尔茨海默病风险。

ABCA7 rare variants and Alzheimer disease risk.

作者信息

机构信息

出版信息

Neurology. 2016 Jun 7;86(23):2134-7. doi: 10.1212/WNL.0000000000002627. Epub 2016 Apr 1.

DOI:10.1212/WNL.0000000000002627

PMID:27037229

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4898320/

Abstract

OBJECTIVE

To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.

METHODS

We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.

RESULTS

CONCLUSIONS

These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.

摘要

目的

在病例对照研究中探讨ABCA7罕见编码变异与阿尔茨海默病（AD）之间的关联。

方法

我们对484例法国早发性AD患者和590例种族匹配的对照进行了全外显子组分析。

结果

结论

这些结果证实ABCA7 LOF变异在AD患者中富集，并将这一发现扩展到预测的有害错义变异。

ABCA7罕见变异与阿尔茨海默病风险。

ABCA7 rare variants and Alzheimer disease risk.

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ABCA7罕见变异与阿尔茨海默病风险。

ABCA7 rare variants and Alzheimer disease risk.

作者信息

机构信息

出版信息

OBJECTIVE

METHODS

RESULTS

CONCLUSIONS

目的

方法

结果

结论