Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Authors:
Francesco Panza, MD, PhD
Francesco Panza, MD, PhD
University of Bari
Geriatrician
Bari | Italy
Pau Pastor
Pau Pastor
University of Navarra
Spain
Valentina Escott-Price Céline Bellenguez Li-San Wang Seung-Hoan Choi Denise Harold Lesley Jones Peter Holmans Amy Gerrish Alexey Vedernikov Alexander Richards Anita L DeStefano Jean-Charles Lambert Carla A Ibrahim-Verbaas Adam C Naj Rebecca Sims Gyungah Jun Joshua C Bis Gary W Beecham Benjamin Grenier-Boley Giancarlo Russo Tricia A Thornton-Wells Nicola Denning Albert V Smith Vincent Chouraki Charlene Thomas M Arfan Ikram Diana Zelenika Badri N Vardarajan Yoichiro Kamatani Chiao-Feng Lin Helena Schmidt Brian Kunkle Melanie L Dunstan Maria Vronskaya Andrew D Johnson Agustin Ruiz Marie-Thérèse Bihoreau Christiane Reitz Florence Pasquier Paul Hollingworth Olivier Hanon Annette L Fitzpatrick Joseph D Buxbaum Dominique Campion Paul K Crane Clinton Baldwin Tim Becker Vilmundur Gudnason Carlos Cruchaga David Craig Najaf Amin Claudine Berr Oscar L Lopez Philip L De Jager Vincent Deramecourt Janet A Johnston Denis Evans Simon Lovestone Luc Letenneur Isabel Hernández David C Rubinsztein Gudny Eiriksdottir Kristel Sleegers Alison M Goate Nathalie Fiévet Matthew J Huentelman Michael Gill Kristelle Brown M Ilyas Kamboh Lina Keller Pascale Barberger-Gateau Bernadette McGuinness Eric B Larson Amanda J Myers Carole Dufouil Stephen Todd David Wallon Seth Love Ekaterina Rogaeva John Gallacher Peter St George-Hyslop Jordi Clarimon Alberto Lleo Anthony Bayer Debby W Tsuang Lei Yu Magda Tsolaki Paola Bossù Gianfranco Spalletta Petra Proitsi John Collinge Sandro Sorbi Florentino Sanchez Garcia Nick C Fox John Hardy Maria Candida Deniz Naranjo Paolo Bosco Robert Clarke Carol Brayne Daniela Galimberti Elio Scarpini Ubaldo Bonuccelli Michelangelo Mancuso Gabriele Siciliano Susanne Moebus Patrizia Mecocci Maria Del Zompo Wolfgang Maier Harald Hampel Alberto Pilotto Ana Frank-García Vincenzo Solfrizzi Paolo Caffarra Benedetta Nacmias William Perry Manuel Mayhaus Lars Lannfelt Hakon Hakonarson Sabrina Pichler Minerva M Carrasquillo Martin Ingelsson Duane Beekly Victoria Alvarez Fanggeng Zou Otto Valladares Steven G Younkin Eliecer Coto Kara L Hamilton-Nelson Wei Gu Cristina Razquin Ignacio Mateo Michael J Owen Kelley M Faber Palmi V Jonsson Onofre Combarros Michael C O'Donovan Laura B Cantwell Hilkka Soininen Deborah Blacker Simon Mead Thomas H Mosley David A Bennett Tamara B Harris Laura Fratiglioni Clive Holmes Renee F A G de Bruijn Peter Passmore Thomas J Montine Karolien Bettens Jerome I Rotter Alexis Brice Kevin Morgan Tatiana M Foroud Walter A Kukull Didier Hannequin John F Powell Michael A Nalls Karen Ritchie Kathryn L Lunetta John S K Kauwe Eric Boerwinkle Matthias Riemenschneider Mercè Boada Mikko Hiltunen Eden R Martin Reinhold Schmidt Dan Rujescu Jean-François Dartigues Richard Mayeux Christophe Tzourio Albert Hofman Markus M Nöthen Caroline Graff Bruce M Psaty Jonathan L Haines Mark Lathrop Margaret A Pericak-Vance Lenore J Launer Christine Van Broeckhoven Lindsay A Farrer Cornelia M van Duijn Alfredo Ramirez Sudha Seshadri Gerard D Schellenberg Philippe Amouyel Julie Williams

PLoS One 2014 12;9(6):e94661. Epub 2014 Jun 12.

Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.

Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.

Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci.

Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055488PMC
October 2015
154 Reads
25 Citations
3.234 Impact Factor

Publication Analysis

Top Keywords

alzheimer's disease
16
susceptibility genes
8
alzheimer's
6
genes
5
reported genes
4
genes detected
4
earlier reported
4
ighv1-67 p = 79×10-8
4
addition earlier
4
findings addition
4
genome-wide loci
4
loci chromosomes
4
chromosomes tp53inp1
4
p = 14×10-6 ighv1-67
4
controlsprincipal findings
4
tp53inp1 p = 14×10-6
4
detected genome-wide
4
alzheimer's cases
4
international genomics
4
genomics alzheimer's
4

Similar Publications