APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Emmanuelle Génin,Didier Hannequin,David Wallon,Kristel Sleegers,Mikko Hiltunen,Onofre Combarros,María J. Bullido,Sebastiaan Engelborghs,P.P. De Deyn,Claudine Berr,Florence Pasquier,Bruno Dubois,Gloria Tognoni,Nathalie Fievet,Nathalie Fievet,Nathalie Brouwers,Karolien Bettens,Beatrice Arosio,Eliecer Coto,M. Del Zompo,Ignacio Mateo,Jacques Epelbaum,Anna Frank-García,Seppo Helisalmi,Elisa Porcellini,Alberto Pilotto,Paola Forti,Raffaele Ferri,Elio Scarpini,Gabriele Siciliano,Vincenzo Solfrizzi,Sandro Sorbi,Gianfranco Spalletta,Fernando Valdivieso,Saila Vepsäläinen,Victoria Alvarez,P. Bosco,Michelangelo Mancuso,Francesco Panza,Benedetta Nacmias,Paola Bossù,Oliver Hanon,Paola Piccardi,Giorgio Annoni,Davide Seripa,Daniela Galimberti,Federico Licastro,Hilkka Soininen,J. F. Dartigues,Kamboh Mi,C. Van Broeckhoven,Jean-Charles Lambert,Jean-Charles Lambert,P. Amouyel,Dominique Campion +54 more
TLDR
Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks as mentioned in this paper.Abstract:
Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.read more
Citations
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Journal ArticleDOI
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
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Genome-wide association study indentifies variants at CLU and CR1 associated with Alzheimer’s disease
J-C Lambert,Simon Heath,G Even,Dominique Campion,K. Sleegers,Mikko Hiltunen,O Cambarros,Diana Zelenika,María J. Bullido,Béatrice Tavernier,Luc Letenneur,Karolien Bettens,Claudine Berr,Florence Pasquier,Nathalie Fievet,P Barbager-Gateau,S. Engelborghs,P.P. De Deyn,Ignacio Mateo,A Franck,Seppo Helisalmi,Elisa Porcellini,Olivier Hanon,M de Pancorbo,Corinne Lendon,Carole Dufouil,C Jaillard,Thierry Léveillard,Alvarez,Paolo Bosco,Michelangelo Mancuso,Francesco Panza,Benedetta Nacmias,Paola Bossù,Paola Piccardi,Giorgio Annoni,Davide Seripa,Daniela Galimberti,Didier Hannequin,Federico Licastro,Hilkka Soininen,Karen Ritchie,Hélène Blanché,J. F. Dartigues,Christophe Tzourio,Ivo Gut,Christine Van Broeckhoven,Annick Alpérovitch,P. Amouyel +48 more
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