Literature DB >> 34482628

Epigenomic features related to microglia are associated with attenuated effect of APOE ε4 on Alzheimer's disease risk in humans.

Yiyi Ma1, Lei Yu2,3, Marta Olah1, Rebecca Smith4, Stephanie R Oatman5, Mariet Allen5, Ehsan Pishva4, Bin Zhang6,7, Vilas Menon1, Nilüfer Ertekin-Taner5,8, Katie Lunnon4, David A Bennett2,3, Hans-Ulrich Klein1, Philip L De Jager1,9.   

Abstract

Not all apolipoprotein E (APOE) ε4 carriers who survive to advanced age develop Alzheimer's disease (AD); factors attenuating the risk of ε4 on AD may exist. Guided by the top ε4-attenuating signals from methylome-wide association analyses (N = 572, ε4+ and ε4-) of neurofibrillary tangles and neuritic plaques, we conducted a meta-analysis for pathological AD within the ε4+ subgroups (N = 235) across four independent collections of brains. Cortical RNA-seq and microglial morphology measurements were used in functional analyses. Three out of the four significant CpG dinucleotides were captured by one principal component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (odds ratio = 2.39, 95% confidence interval = [1.64,3.46], P = 7.08 × 10-6 ). An epigenomic factor associated with a reduced proportion of activated microglia (epigenomic factor of activated microglia, EFAM) appears to attenuate the risk of ε4 on AD.
© 2021 the Alzheimer's Association.

Entities:  

Keywords:  Alzheimer's disease; apolipoprotein E; epigenome; microglia

Mesh：

Substances：

Year:  2021        PMID： 34482628      PMCID： PMC9475136          DOI： 10.1002/alz.12425

Source DB:  PubMed          Journal:  Alzheimers Dement        ISSN： 1552-5260            Impact factor:   16.655


  29 in total

1.  Overview and findings from the rush Memory and Aging Project.

Authors:  David A Bennett; Julie A Schneider; Aron S Buchman; Lisa L Barnes; Patricia A Boyle; Robert S Wilson
Journal:  Curr Alzheimer Res       Date:  2012-07       Impact factor: 3.498

2.  Chromosome conformation elucidates regulatory relationships in developing human brain.

Authors:  Hyejung Won; Luis de la Torre-Ubieta; Jason L Stein; Neelroop N Parikshak; Jerry Huang; Carli K Opland; Michael J Gandal; Gavin J Sutton; Farhad Hormozdiari; Daning Lu; Changhoon Lee; Eleazar Eskin; Irina Voineagu; Jason Ernst; Daniel H Geschwind
Journal:  Nature       Date:  2016-10-19       Impact factor: 49.962

3.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.

Authors:  L A Farrer; L A Cupples; J L Haines; B Hyman; W A Kukull; R Mayeux; R H Myers; M A Pericak-Vance; N Risch; C M van Duijn
Journal:  JAMA       Date:  1997 Oct 22-29       Impact factor: 56.272

4.  Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants.

Authors:  Fanggeng Zou; High Seng Chai; Curtis S Younkin; Mariet Allen; Julia Crook; V Shane Pankratz; Minerva M Carrasquillo; Christopher N Rowley; Asha A Nair; Sumit Middha; Sooraj Maharjan; Thuy Nguyen; Li Ma; Kimberly G Malphrus; Ryan Palusak; Sarah Lincoln; Gina Bisceglio; Constantin Georgescu; Naomi Kouri; Christopher P Kolbert; Jin Jen; Jonathan L Haines; Richard Mayeux; Margaret A Pericak-Vance; Lindsay A Farrer; Gerard D Schellenberg; Ronald C Petersen; Neill R Graff-Radford; Dennis W Dickson; Steven G Younkin; Nilüfer Ertekin-Taner
Journal:  PLoS Genet       Date:  2012-06-07       Impact factor: 5.917

5.  Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Authors:  Brian W Kunkle; Benjamin Grenier-Boley; Rebecca Sims; Joshua C Bis; Vincent Damotte; Adam C Naj; Anne Boland; Maria Vronskaya; Sven J van der Lee; Alexandre Amlie-Wolf; Céline Bellenguez; Aura Frizatti; Vincent Chouraki; Eden R Martin; Kristel Sleegers; Nandini Badarinarayan; Johanna Jakobsdottir; Kara L Hamilton-Nelson; Sonia Moreno-Grau; Robert Olaso; Rachel Raybould; Yuning Chen; Amanda B Kuzma; Mikko Hiltunen; Taniesha Morgan; Shahzad Ahmad; Badri N Vardarajan; Jacques Epelbaum; Per Hoffmann; Merce Boada; Gary W Beecham; Jean-Guillaume Garnier; Denise Harold; Annette L Fitzpatrick; Otto Valladares; Marie-Laure Moutet; Amy Gerrish; Albert V Smith; Liming Qu; Delphine Bacq; Nicola Denning; Xueqiu Jian; Yi Zhao; Maria Del Zompo; Nick C Fox; Seung-Hoan Choi; Ignacio Mateo; Joseph T Hughes; Hieab H Adams; John Malamon; Florentino Sanchez-Garcia; Yogen Patel; Jennifer A Brody; Beth A Dombroski; Maria Candida Deniz Naranjo; Makrina Daniilidou; Gudny Eiriksdottir; Shubhabrata Mukherjee; David Wallon; James Uphill; Thor Aspelund; Laura B Cantwell; Fabienne Garzia; Daniela Galimberti; Edith Hofer; Mariusz Butkiewicz; Bertrand Fin; Elio Scarpini; Chloe Sarnowski; Will S Bush; Stéphane Meslage; Johannes Kornhuber; Charles C White; Yuenjoo Song; Robert C Barber; Sebastiaan Engelborghs; Sabrina Sordon; Dina Voijnovic; Perrie M Adams; Rik Vandenberghe; Manuel Mayhaus; L Adrienne Cupples; Marilyn S Albert; Peter P De Deyn; Wei Gu; Jayanadra J Himali; Duane Beekly; Alessio Squassina; Annette M Hartmann; Adelina Orellana; Deborah Blacker; Eloy Rodriguez-Rodriguez; Simon Lovestone; Melissa E Garcia; Rachelle S Doody; Carmen Munoz-Fernadez; Rebecca Sussams; Honghuang Lin; Thomas J Fairchild; Yolanda A Benito; Clive Holmes; Hata Karamujić-Čomić; Matthew P Frosch; Hakan Thonberg; Wolfgang Maier; Gennady Roshchupkin; Bernardino Ghetti; Vilmantas Giedraitis; Amit Kawalia; Shuo Li; Ryan M Huebinger; Lena Kilander; Susanne Moebus; Isabel Hernández; M Ilyas Kamboh; RoseMarie Brundin; James Turton; Qiong Yang; Mindy J Katz; Letizia Concari; Jenny Lord; Alexa S Beiser; C Dirk Keene; Seppo Helisalmi; Iwona Kloszewska; Walter A Kukull; Anne Maria Koivisto; Aoibhinn Lynch; Lluís Tarraga; Eric B Larson; Annakaisa Haapasalo; Brian Lawlor; Thomas H Mosley; Richard B Lipton; Vincenzo Solfrizzi; Michael Gill; W T Longstreth; Thomas J Montine; Vincenza Frisardi; Monica Diez-Fairen; Fernando Rivadeneira; Ronald C Petersen; Vincent Deramecourt; Ignacio Alvarez; Francesca Salani; Antonio Ciaramella; Eric Boerwinkle; Eric M Reiman; Nathalie Fievet; Jerome I Rotter; Joan S Reisch; Olivier Hanon; Chiara Cupidi; A G Andre Uitterlinden; Donald R Royall; Carole Dufouil; Raffaele Giovanni Maletta; Itziar de Rojas; Mary Sano; Alexis Brice; Roberta Cecchetti; Peter St George-Hyslop; Karen Ritchie; Magda Tsolaki; Debby W Tsuang; Bruno Dubois; David Craig; Chuang-Kuo Wu; Hilkka Soininen; Despoina Avramidou; Roger L Albin; Laura Fratiglioni; Antonia Germanou; Liana G Apostolova; Lina Keller; Maria Koutroumani; Steven E Arnold; Francesco Panza; Olymbia Gkatzima; Sanjay Asthana; Didier Hannequin; Patrice Whitehead; Craig S Atwood; Paolo Caffarra; Harald Hampel; Inés Quintela; Ángel Carracedo; Lars Lannfelt; David C Rubinsztein; Lisa L Barnes; Florence Pasquier; Lutz Frölich; Sandra Barral; Bernadette McGuinness; Thomas G Beach; Janet A Johnston; James T Becker; Peter Passmore; Eileen H Bigio; Jonathan M Schott; Thomas D Bird; Jason D Warren; Bradley F Boeve; Michelle K Lupton; James D Bowen; Petra Proitsi; Adam Boxer; John F Powell; James R Burke; John S K Kauwe; Jeffrey M Burns; Michelangelo Mancuso; Joseph D Buxbaum; Ubaldo Bonuccelli; Nigel J Cairns; Andrew McQuillin; Chuanhai Cao; Gill Livingston; Chris S Carlson; Nicholas J Bass; Cynthia M Carlsson; John Hardy; Regina M Carney; Jose Bras; Minerva M Carrasquillo; Rita Guerreiro; Mariet Allen; Helena C Chui; Elizabeth Fisher; Carlo Masullo; Elizabeth A Crocco; Charles DeCarli; Gina Bisceglio; Malcolm Dick; Li Ma; Ranjan Duara; Neill R Graff-Radford; Denis A Evans; Angela Hodges; Kelley M Faber; Martin Scherer; Kenneth B Fallon; Matthias Riemenschneider; David W Fardo; Reinhard Heun; Martin R Farlow; Heike Kölsch; Steven Ferris; Markus Leber; Tatiana M Foroud; Isabella Heuser; Douglas R Galasko; Ina Giegling; Marla Gearing; Michael Hüll; Daniel H Geschwind; John R Gilbert; John Morris; Robert C Green; Kevin Mayo; John H Growdon; Thomas Feulner; Ronald L Hamilton; Lindy E Harrell; Dmitriy Drichel; Lawrence S Honig; Thomas D Cushion; Matthew J Huentelman; Paul Hollingworth; Christine M Hulette; Bradley T Hyman; Rachel Marshall; Gail P Jarvik; Alun Meggy; Erin Abner; Georgina E Menzies; Lee-Way Jin; Ganna Leonenko; Luis M Real; Gyungah R Jun; Clinton T Baldwin; Detelina Grozeva; Anna Karydas; Giancarlo Russo; Jeffrey A Kaye; Ronald Kim; Frank Jessen; Neil W Kowall; Bruno Vellas; Joel H Kramer; Emma Vardy; Frank M LaFerla; Karl-Heinz Jöckel; James J Lah; Martin Dichgans; James B Leverenz; David Mann; Allan I Levey; Stuart Pickering-Brown; Andrew P Lieberman; Norman Klopp; Kathryn L Lunetta; H-Erich Wichmann; Constantine G Lyketsos; Kevin Morgan; Daniel C Marson; Kristelle Brown; Frank Martiniuk; Christopher Medway; Deborah C Mash; Markus M Nöthen; Eliezer Masliah; Nigel M Hooper; Wayne C McCormick; Antonio Daniele; Susan M McCurry; Anthony Bayer; Andrew N McDavid; John Gallacher; Ann C McKee; Hendrik van den Bussche; Marsel Mesulam; Carol Brayne; Bruce L Miller; Steffi Riedel-Heller; Carol A Miller; Joshua W Miller; Ammar Al-Chalabi; John C Morris; Christopher E Shaw; Amanda J Myers; Jens Wiltfang; Sid O'Bryant; John M Olichney; Victoria Alvarez; Joseph E Parisi; Andrew B Singleton; Henry L Paulson; John Collinge; William R Perry; Simon Mead; Elaine Peskind; David H Cribbs; Martin Rossor; Aimee Pierce; Natalie S Ryan; Wayne W Poon; Benedetta Nacmias; Huntington Potter; Sandro Sorbi; Joseph F Quinn; Eleonora Sacchinelli; Ashok Raj; Gianfranco Spalletta; Murray Raskind; Carlo Caltagirone; Paola Bossù; Maria Donata Orfei; Barry Reisberg; Robert Clarke; Christiane Reitz; A David Smith; John M Ringman; Donald Warden; Erik D Roberson; Gordon Wilcock; Ekaterina Rogaeva; Amalia Cecilia Bruni; Howard J Rosen; Maura Gallo; Roger N Rosenberg; Yoav Ben-Shlomo; Mark A Sager; Patrizia Mecocci; Andrew J Saykin; Pau Pastor; Michael L Cuccaro; Jeffery M Vance; Julie A Schneider; Lori S Schneider; Susan Slifer; William W Seeley; Amanda G Smith; Joshua A Sonnen; Salvatore Spina; Robert A Stern; Russell H Swerdlow; Mitchell Tang; Rudolph E Tanzi; John Q Trojanowski; Juan C Troncoso; Vivianna M Van Deerlin; Linda J Van Eldik; Harry V Vinters; Jean Paul Vonsattel; Sandra Weintraub; Kathleen A Welsh-Bohmer; Kirk C Wilhelmsen; Jennifer Williamson; Thomas S Wingo; Randall L Woltjer; Clinton B Wright; Chang-En Yu; Lei Yu; Yasaman Saba; Alberto Pilotto; Maria J Bullido; Oliver Peters; Paul K Crane; David Bennett; Paola Bosco; Eliecer Coto; Virginia Boccardi; Phil L De Jager; Alberto Lleo; Nick Warner; Oscar L Lopez; Martin Ingelsson; Panagiotis Deloukas; Carlos Cruchaga; Caroline Graff; Rhian Gwilliam; Myriam Fornage; Alison M Goate; Pascual Sanchez-Juan; Patrick G Kehoe; Najaf Amin; Nilifur Ertekin-Taner; Claudine Berr; Stéphanie Debette; Seth Love; Lenore J Launer; Steven G Younkin; Jean-Francois Dartigues; Chris Corcoran; M Arfan Ikram; Dennis W Dickson; Gael Nicolas; Dominique Campion; JoAnn Tschanz; Helena Schmidt; Hakon Hakonarson; Jordi Clarimon; Ron Munger; Reinhold Schmidt; Lindsay A Farrer; Christine Van Broeckhoven; Michael C O'Donovan; Anita L DeStefano; Lesley Jones; Jonathan L Haines; Jean-Francois Deleuze; Michael J Owen; Vilmundur Gudnason; Richard Mayeux; Valentina Escott-Price; Bruce M Psaty; Alfredo Ramirez; Li-San Wang; Agustin Ruiz; Cornelia M van Duijn; Peter A Holmans; Sudha Seshadri; Julie Williams; Phillippe Amouyel; Gerard D Schellenberg; Jean-Charles Lambert; Margaret A Pericak-Vance
Journal:  Nat Genet       Date:  2019-02-28       Impact factor: 41.307

6.  A novel Alzheimer disease locus located near the gene encoding tau protein.

Authors:  G Jun; C A Ibrahim-Verbaas; M Vronskaya; J-C Lambert; J Chung; A C Naj; B W Kunkle; L-S Wang; J C Bis; C Bellenguez; D Harold; K L Lunetta; A L Destefano; B Grenier-Boley; R Sims; G W Beecham; A V Smith; V Chouraki; K L Hamilton-Nelson; M A Ikram; N Fievet; N Denning; E R Martin; H Schmidt; Y Kamatani; M L Dunstan; O Valladares; A R Laza; D Zelenika; A Ramirez; T M Foroud; S-H Choi; A Boland; T Becker; W A Kukull; S J van der Lee; F Pasquier; C Cruchaga; D Beekly; A L Fitzpatrick; O Hanon; M Gill; R Barber; V Gudnason; D Campion; S Love; D A Bennett; N Amin; C Berr; Magda Tsolaki; J D Buxbaum; O L Lopez; V Deramecourt; N C Fox; L B Cantwell; L Tárraga; C Dufouil; J Hardy; P K Crane; G Eiriksdottir; D Hannequin; R Clarke; D Evans; T H Mosley; L Letenneur; C Brayne; W Maier; P De Jager; V Emilsson; J-F Dartigues; H Hampel; M I Kamboh; R F A G de Bruijn; C Tzourio; P Pastor; E B Larson; J I Rotter; M C O'Donovan; T J Montine; M A Nalls; S Mead; E M Reiman; P V Jonsson; C Holmes; P H St George-Hyslop; M Boada; P Passmore; J R Wendland; R Schmidt; K Morgan; A R Winslow; J F Powell; M Carasquillo; S G Younkin; J Jakobsdóttir; J S K Kauwe; K C Wilhelmsen; D Rujescu; M M Nöthen; A Hofman; L Jones; J L Haines; B M Psaty; C Van Broeckhoven; P Holmans; L J Launer; R Mayeux; M Lathrop; A M Goate; V Escott-Price; S Seshadri; M A Pericak-Vance; P Amouyel; J Williams; C M van Duijn; G D Schellenberg; L A Farrer
Journal:  Mol Psychiatry       Date:  2015-03-17       Impact factor: 15.992

7.  Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases.

Authors:  Mariet Allen; Minerva M Carrasquillo; Cory Funk; Benjamin D Heavner; Fanggeng Zou; Curtis S Younkin; Jeremy D Burgess; High-Seng Chai; Julia Crook; James A Eddy; Hongdong Li; Ben Logsdon; Mette A Peters; Kristen K Dang; Xue Wang; Daniel Serie; Chen Wang; Thuy Nguyen; Sarah Lincoln; Kimberly Malphrus; Gina Bisceglio; Ma Li; Todd E Golde; Lara M Mangravite; Yan Asmann; Nathan D Price; Ronald C Petersen; Neill R Graff-Radford; Dennis W Dickson; Steven G Younkin; Nilüfer Ertekin-Taner
Journal:  Sci Data       Date:  2016-10-11       Impact factor: 6.444

8.  Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data.

Authors:  Charles C White; Hyun-Sik Yang; Lei Yu; Lori B Chibnik; Robert J Dawe; Jingyun Yang; Hans-Ulrich Klein; Daniel Felsky; Alfredo Ramos-Miguel; Konstantinos Arfanakis; William G Honer; Reisa A Sperling; Julie A Schneider; David A Bennett; Philip L De Jager
Journal:  PLoS Med       Date:  2017-04-25       Impact factor: 11.069

9.  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Authors:  J C Lambert; C A Ibrahim-Verbaas; D Harold; A C Naj; R Sims; C Bellenguez; A L DeStafano; J C Bis; G W Beecham; B Grenier-Boley; G Russo; T A Thorton-Wells; N Jones; A V Smith; V Chouraki; C Thomas; M A Ikram; D Zelenika; B N Vardarajan; Y Kamatani; C F Lin; A Gerrish; H Schmidt; B Kunkle; M L Dunstan; A Ruiz; M T Bihoreau; S H Choi; C Reitz; F Pasquier; C Cruchaga; D Craig; N Amin; C Berr; O L Lopez; P L De Jager; V Deramecourt; J A Johnston; D Evans; S Lovestone; L Letenneur; F J Morón; D C Rubinsztein; G Eiriksdottir; K Sleegers; A M Goate; N Fiévet; M W Huentelman; M Gill; K Brown; M I Kamboh; L Keller; P Barberger-Gateau; B McGuiness; E B Larson; R Green; A J Myers; C Dufouil; S Todd; D Wallon; S Love; E Rogaeva; J Gallacher; P St George-Hyslop; J Clarimon; A Lleo; A Bayer; D W Tsuang; L Yu; M Tsolaki; P Bossù; G Spalletta; P Proitsi; J Collinge; S Sorbi; F Sanchez-Garcia; N C Fox; J Hardy; M C Deniz Naranjo; P Bosco; R Clarke; C Brayne; D Galimberti; M Mancuso; F Matthews; S Moebus; P Mecocci; M Del Zompo; W Maier; H Hampel; A Pilotto; M Bullido; F Panza; P Caffarra; B Nacmias; J R Gilbert; M Mayhaus; L Lannefelt; H Hakonarson; S Pichler; M M Carrasquillo; M Ingelsson; D Beekly; V Alvarez; F Zou; O Valladares; S G Younkin; E Coto; K L Hamilton-Nelson; W Gu; C Razquin; P Pastor; I Mateo; M J Owen; K M Faber; P V Jonsson; O Combarros; M C O'Donovan; L B Cantwell; H Soininen; D Blacker; S Mead; T H Mosley; D A Bennett; T B Harris; L Fratiglioni; C Holmes; R F de Bruijn; P Passmore; T J Montine; K Bettens; J I Rotter; A Brice; K Morgan; T M Foroud; W A Kukull; D Hannequin; J F Powell; M A Nalls; K Ritchie; K L Lunetta; J S Kauwe; E Boerwinkle; M Riemenschneider; M Boada; M Hiltuenen; E R Martin; R Schmidt; D Rujescu; L S Wang; J F Dartigues; R Mayeux; C Tzourio; A Hofman; M M Nöthen; C Graff; B M Psaty; L Jones; J L Haines; P A Holmans; M Lathrop; M A Pericak-Vance; L J Launer; L A Farrer; C M van Duijn; C Van Broeckhoven; V Moskvina; S Seshadri; J Williams; G D Schellenberg; P Amouyel
Journal:  Nat Genet       Date:  2013-10-27       Impact factor: 38.330

10.  A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research.

Authors:  Philip L De Jager; Yiyi Ma; Cristin McCabe; Jishu Xu; Badri N Vardarajan; Daniel Felsky; Hans-Ulrich Klein; Charles C White; Mette A Peters; Ben Lodgson; Parham Nejad; Anna Tang; Lara M Mangravite; Lei Yu; Chris Gaiteri; Sara Mostafavi; Julie A Schneider; David A Bennett
Journal:  Sci Data       Date:  2018-08-07       Impact factor: 6.444
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  3 in total

Review 1.  Kynurenine Pathway Metabolites as Biomarkers in Alzheimer's Disease.

Authors:  Yuqing Liang; Shan Xie; Yanyun He; Manru Xu; Xi Qiao; Yue Zhu; Wenbin Wu
Journal:  Dis Markers       Date:  2022-01-19       Impact factor: 3.434

Review 2.  Epigenetics in Alzheimer's Disease.

Authors:  Xiaodie Gao; Qiang Chen; Hua Yao; Jie Tan; Zheng Liu; Yan Zhou; Zhenyou Zou
Journal:  Front Aging Neurosci       Date:  2022-06-23       Impact factor: 5.702

3.  Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer's disease.

Authors:  Tiago C Silva; Juan I Young; Lanyu Zhang; Lissette Gomez; Michael A Schmidt; Achintya Varma; X Steven Chen; Eden R Martin; Lily Wang
Journal:  Nat Commun       Date:  2022-08-18       Impact factor: 17.694
  3 in total

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