Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype

Ma Yiyi; Jun Gyungah R.; Zhang Xiaoling; No Adam C.; Chen Yuning; Bellenguez Celine; Hamilton-Nelson Kara; Debette Stephanie; DeStefano Anita L.; Nicolas Gael; Bennett David A.; Lambert Jean-Charles; Grenier-Boley Benjamin; Charbonnier Camille; Quenez Olivier; Chauhan Ganesh; Wallon David; Rousseau Stephan; Richard Anne Claire; Boland Anne; Bourque Guillaume; Munter Hans Markus; Olaso Robert; Meyer Vincent; Rollin-Sillaire Adeline; Pasquier Florence; Letenneur Luc; Redon Richard; Dartigues Jean-Francois; Tzourio Christophe; Lathrop Mark; Deleuze Jean-Francois; Hannequin Didier; Genin Emmanuelle; Amouyel Philippe; Campion Dominique; Bellair Michelle; Huyen Dinh; Doddapeneni Harsha; Dugan-Perez Shannon; English Adam; Gibbs Richard A.; Han Yi; Hu Jianhong; Jayaseelan Joy; Kalra Divya; Khan Ziad; Korchina Viktoriya; Lee Sandra; Liu Yue; Liu Xiuping; Muzny Donna; Nasser Waleed; Salerno William; Santibanez Jireh; Skinner Evette; White Simon; Worley Kim; Zhu Yingmin; Beiser Alexa; Chung Jaeyoon; Cupples Adrienne; DeStefano Anita; Dupuis Josee; Farrell John; Lancour Daniel; Lin Honghuang; Liu Ching Ti; Lunetta Kathy L.; Patel Devanshi; Sarnowski Chloe; Satizabal Claudia; Seshadri Sudha; Sun Fangui Jenny; Choi Seung Hoan; Banks Eric; Gabriel Stacey; Gupta Namrata; Bush William S.; Butkiewicz Mariusz; Haines Jonathan L.; Smieszek Sandra; Song Yeunjoo; Barral Sandra; DeJager Phillip L.; Mayeux Richard; Reitz Christiane; Reyes Dolly; Tosto Giuseppe; Vardarajan Badri N.; Amad Shahzad; Amin Najaf; Ikram Afran; van der Lee Sven; van Duijn Cornelia; van der Spek Ashley; Schmidt Helena; Schmidt Reinhold; Goate Alison; Kapoor Manav; Marcora Edoardo; Renton Alan; Faber Kelley M.; Foroud Tatiana; Feolo Michael; Stine Adam; Launer Lenore J.; Xia Li Charlie; Beecham Gary W.; Hamilton-Nelson Kara L.; Jaworski James; Kunkle Brian W.; Martin Eden R.; Pericak-Vance Margaret A.; Rajabli Laid; Schmidt Michael; Mosley Thomas H.; Cantwell Laura B.; Childress Micah; Chou Yi-Fan; Cweibel Rebecca; Gangadharan Prabhakaran; Kuzma Amanda P.; Leung Yuk Yee; Lin Han-Jen; Malamon John; Mlynarski Elisabeth; Naj Adam C.; Qu Liming; Schellenberg Gerard D.; Valladares Otto; Wang Li-San; Wang Weixin; Zhang Nancy; Below Jennifer E.; Boerwinkle Eric; Bressler Jan; Fornage Myriam; Jian Xueqiu; Liu Xiaoming; Bis Joshua C.; Blue Elizabeth; Brown Lisa; Day Tyler; Dorschner Michael; Horimoto Andrea R.; Nafikov Rafael A.; Nato Alejandro Q. Jr.; Navas Patrick; Hiep Nguyen; Psaty Bruce; Rice Kenneth; Saad Mohamad; Sohi Harkirat; Thornton Timothy; Tsuang Debby; Wang Bowen; Wijsman Ellen; Witten Daniela; Antonacd-Fulton Lucinda; Appelbaum Elizabeth; Cruchaga Carlos; Fulton Robert S.; Koboldt Daniel C.; Larson David E.; Waligorski Jason; Wilson Richard K.; Bowen James D.; Crane Paul K.; Jarvik Gail P.; Keene C. Dirk; Larson Eric B.; Lee W. William; McCornick Wayne C.; McCurry Susan M.; Mukherjee Shubhabrata; Richmire Katie Rose; Benke Thomas; Dal-Bianco Peter; Hofer Edith; Ransmayr Gerhard; Saba Yasaman; Becker James T.; Fitzpatrick Annette L.; Kamboh M. Ilyas; Kuller Lewis H.; Longstreth W. T. Jr.; Lopez Oscar L.; Psaty Bruce M.; Rotter Jerome I; De Jager Philip L.; Evans Denis A.; Adams Hieab H.; Comic Hata; Hofman Albert; Koudstaal Peter J.; Rivadeneira Fernando; Uitterlinden Andre G.; Lantigua Rafael; Medrano Martin; Reyes-Dumeyer Dolly; Vardarajan Badri; Reiser Alexa S.; Chouraki Vincent; Himali Jayanadra J.; White Charles C.; Beekly Duane; Bowen James; Kukull Walter A.; McCormick Wayne; Teri Linda; Carrasquillo Minerva M.; Dickson Dennis W.; Ertekin-Taner Nilufer; Graff-Radford Neill R.; Parisi Joseph E.; Petersen Ronald C.; Younkin Steven G.; Duara Ranjan; Foroud Tatiana M.; Lipton Richard B.; Scott Bill; Vance Jeffery M.; Auerbach Sanford; Chui Helan; Cupples L. Adrienne; DeCarli Charles; Farlow Martin; Farrer Lindsay A.; Friedland Robert; Go Rodney C. P.; Green Robert C.; Griffith Patrick; Growdon John; Kukull Walter; Kurz Alexander; Logue Mark; Lunetta Kathryn L.; Obisesan Thomas; Petrovitch Helen; Sabbagh Marwan; Sadovnick A. Dessa; Tsolaki Magda; Bertelsen Sarah; Bird Thomas D.; Boeve Bradley F.; Faber Kelley; Goate Alison M.; Ottman Ruth; Rosenberg Roger; Schaid Daniel; Sweet Robert A.; Abner Erin; Albert Marilyn S.; Albin Roger L.; Apostolova Liana G.; Asthana Sanjay; Atwood Craig S.; Barnes Lisa L.; Beach Thomas G.; Bigio Eileen H.; Blacker Deborah; Boxer Adam; Brewer James B.; Burke James R.; Burns Jeffrey M.; Buxbaum Joseph D.; Cairns Nigel J.; Cao Chuanhai; Carlsson Cynthia M.; Caselli Richard J.; Chui Helena C.; de Leon Mony; Dick Malcolm; Fardo David W.; Farlow Martin R.; Ferris Steven; Frosch Matthew P.; Galasko Douglas R.; Gearing Marla; Geldmacher David S.; Geschwind Daniel H.; Ghetti Bernardino; Gleason Carey; Gomez-Isla Teresa; Grabowski Thomas; Growdon John H.; Honig Lawrence S.; Huebinger Ryan M.; Huentelman Matthew J.; Hulette Christine M.; Hyman Bradley T.; Jayadev Suman; Jin Lee-Way; Johnson Sterling; Karydas Anna; Kaye Jeffrey A.; Kim Ronald; Kowall Neil W.; Kramer Joel H.; LaFerla Frank M.; Lah James J.; Levey Allan I; Li Ge; Lieberman Andrew P.; Lyketsos Constantine G.; Marson Daniel C.; McKee Ann C.; Mesulam Marsel; Mez Jesse; Miller Bruce L.; Miller Carol A.; Moghekar Abhay; Morris John C.; Olichney John M.; Paulson Henry L.; Peskind Elaine; Pierce Aimee; Poon Wayne W.; Puglielli Luigi; Quinn Joseph F.; Raj Ashok; Raskind Murray; Reiman Eric M.; Reisberg Barry; Rissman Robert A.; Roberson Erik D.; Rosen Howard J.; Rosenberg Roger N.; Sadowski Martin; Sager Mark A.; Salmon David P.; Sano Mary; Saykin Andrew J.; Schneider Julie A.; Schneider Lon S.; Seeley William W.; Small Scott; Smith Amanda G.; Stern Robert A.; Swerdlow Russell H.; Tanzi Rudolph E.; Farias Sarah E. 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首页> 外文期刊>JAMA neurology >Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype

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Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype

机译：Apoe基因型分层的阿尔茨海默病全外膜序列测序数据分析

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Key PointsQuestionAre there rare variants associated with Alzheimer disease among individuals who possess or lack the APOE epsilon 4 allele? FindingsThis case-control, whole-exome sequencing study of 10441 individuals identified a possibly novel association with a GPAA1 variant among those who lacked the APOE epsilon 4 allele, a finding that was replicated in independent data sets and supported by analyses of whole-genome and RNA sequencing data derived from human brain tissue. Novel associations were identified among individuals with the APOE epsilon 4 allele for variants in ISYNA1, OR8G5, IGHV3-7, and SLC24A3. MeaningThis study supports the apparent involvement of genes in Alzheimer disease whose effects are dependent on APOE genotype.

机译：关键点查询是有与阿尔茨海默病有关的罕见变体，他们拥有或缺乏apsilon 4等位基因的个人？ Findingsthis案例控制，10441个体的全外膜测序研究发现了与缺少Aposilon 4等位基因的人的GPAA1变体，一个可能是在独立数据集中复制的发现，并通过全基因组的分析支持来自人脑组织的RNA测序数据。在ISYNA1，OR8G5，IGHV3-7和SLC24A3中具有APOE EPSILON 4等位基因的个体中鉴定新的缔组织。意思研究支持基因在阿尔茨海默病中的表观依赖，其作用依赖于ApoE基因型。

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《JAMA neurology》 |2019年第9期|共10页
作者
Ma Yiyi; Jun Gyungah R.; Zhang Xiaoling; No Adam C.; Chen Yuning; Bellenguez Celine; Hamilton-Nelson Kara; Debette Stephanie; DeStefano Anita L.; Nicolas Gael; Bennett David A.; Lambert Jean-Charles; Grenier-Boley Benjamin; Charbonnier Camille; Quenez Olivier; Chauhan Ganesh; Wallon David; Rousseau Stephan; Richard Anne Claire; Boland Anne; Bourque Guillaume; Munter Hans Markus; Olaso Robert; Meyer Vincent; Rollin-Sillaire Adeline; Pasquier Florence; Letenneur Luc; Redon Richard; Dartigues Jean-Francois; Tzourio Christophe; Lathrop Mark; Deleuze Jean-Francois; Hannequin Didier; Genin Emmanuelle; Amouyel Philippe; Campion Dominique; Bellair Michelle; Huyen Dinh; Doddapeneni Harsha; Dugan-Perez Shannon; English Adam; Gibbs Richard A.; Han Yi; Hu Jianhong; Jayaseelan Joy; Kalra Divya; Khan Ziad; Korchina Viktoriya; Lee Sandra; Liu Yue; Liu Xiuping; Muzny Donna; Nasser Waleed; Salerno William; Santibanez Jireh; Skinner Evette; White Simon; Worley Kim; Zhu Yingmin; Beiser Alexa; Chung Jaeyoon; Cupples Adrienne; DeStefano Anita; Dupuis Josee; Farrell John; Lancour Daniel; Lin Honghuang; Liu Ching Ti; Lunetta Kathy L.; Patel Devanshi; Sarnowski Chloe; Satizabal Claudia; Seshadri Sudha; Sun Fangui Jenny; Choi Seung Hoan; Banks Eric; Gabriel Stacey; Gupta Namrata; Bush William S.; Butkiewicz Mariusz; Haines Jonathan L.; Smieszek Sandra; Song Yeunjoo; Barral Sandra; DeJager Phillip L.; Mayeux Richard; Reitz Christiane; Reyes Dolly; Tosto Giuseppe; Vardarajan Badri N.; Amad Shahzad; Amin Najaf; Ikram Afran; van der Lee Sven; van Duijn Cornelia; van der Spek Ashley; Schmidt Helena; Schmidt Reinhold; Goate Alison; Kapoor Manav; Marcora Edoardo; Renton Alan; Faber Kelley M.; Foroud Tatiana; Feolo Michael; Stine Adam; Launer Lenore J.; Xia Li Charlie; Beecham Gary W.; Hamilton-Nelson Kara L.; Jaworski James; Kunkle Brian W.; Martin Eden R.; Pericak-Vance Margaret A.; Rajabli Laid; Schmidt Michael; Mosley Thomas H.; Cantwell Laura B.; Childress Micah; Chou Yi-Fan; Cweibel Rebecca; Gangadharan Prabhakaran; Kuzma Amanda P.; Leung Yuk Yee; Lin Han-Jen; Malamon John; Mlynarski Elisabeth; Naj Adam C.; Qu Liming; Schellenberg Gerard D.; Valladares Otto; Wang Li-San; Wang Weixin; Zhang Nancy; Below Jennifer E.; Boerwinkle Eric; Bressler Jan; Fornage Myriam; Jian Xueqiu; Liu Xiaoming; Bis Joshua C.; Blue Elizabeth; Brown Lisa; Day Tyler; Dorschner Michael; Horimoto Andrea R.; Nafikov Rafael A.; Nato Alejandro Q. Jr.; Navas Patrick; Hiep Nguyen; Psaty Bruce; Rice Kenneth; Saad Mohamad; Sohi Harkirat; Thornton Timothy; Tsuang Debby; Wang Bowen; Wijsman Ellen; Witten Daniela; Antonacd-Fulton Lucinda; Appelbaum Elizabeth; Cruchaga Carlos; Fulton Robert S.; Koboldt Daniel C.; Larson David E.; Waligorski Jason; Wilson Richard K.; Bowen James D.; Crane Paul K.; Jarvik Gail P.; Keene C. Dirk; Larson Eric B.; Lee W. William; McCornick Wayne C.; McCurry Susan M.; Mukherjee Shubhabrata; Richmire Katie Rose; Benke Thomas; Dal-Bianco Peter; Hofer Edith; Ransmayr Gerhard; Saba Yasaman; Becker James T.; Fitzpatrick Annette L.; Kamboh M. Ilyas; Kuller Lewis H.; Longstreth W. T. Jr.; Lopez Oscar L.; Psaty Bruce M.; Rotter Jerome I; De Jager Philip L.; Evans Denis A.; Adams Hieab H.; Comic Hata; Hofman Albert; Koudstaal Peter J.; Rivadeneira Fernando; Uitterlinden Andre G.; Lantigua Rafael; Medrano Martin; Reyes-Dumeyer Dolly; Vardarajan Badri; Reiser Alexa S.; Chouraki Vincent; Himali Jayanadra J.; White Charles C.; Beekly Duane; Bowen James; Kukull Walter A.; McCormick Wayne; Teri Linda; Carrasquillo Minerva M.; Dickson Dennis W.; Ertekin-Taner Nilufer; Graff-Radford Neill R.; Parisi Joseph E.; Petersen Ronald C.; Younkin Steven G.; Duara Ranjan; Foroud Tatiana M.; Lipton Richard B.; Scott Bill; Vance Jeffery M.; Auerbach Sanford; Chui Helan; Cupples L. Adrienne; DeCarli Charles; Farlow Martin; Farrer Lindsay A.; Friedland Robert; Go Rodney C. P.; Green Robert C.; Griffith Patrick; Growdon John; Kukull Walter; Kurz Alexander; Logue Mark; Lunetta Kathryn L.; Obisesan Thomas; Petrovitch Helen; Sabbagh Marwan; Sadovnick A. Dessa; Tsolaki Magda; Bertelsen Sarah; Bird Thomas D.; Boeve Bradley F.; Faber Kelley; Goate Alison M.; Ottman Ruth; Rosenberg Roger; Schaid Daniel; Sweet Robert A.; Abner Erin; Albert Marilyn S.; Albin Roger L.; Apostolova Liana G.; Asthana Sanjay; Atwood Craig S.; Barnes Lisa L.; Beach Thomas G.; Bigio Eileen H.; Blacker Deborah; Boxer Adam; Brewer James B.; Burke James R.; Burns Jeffrey M.; Buxbaum Joseph D.; Cairns Nigel J.; Cao Chuanhai; Carlsson Cynthia M.; Caselli Richard J.; Chui Helena C.; de Leon Mony; Dick Malcolm; Fardo David W.; Farlow Martin R.; Ferris Steven; Frosch Matthew P.; Galasko Douglas R.; Gearing Marla; Geldmacher David S.; Geschwind Daniel H.; Ghetti Bernardino; Gleason Carey; Gomez-Isla Teresa; Grabowski Thomas; Growdon John H.; Honig Lawrence S.; Huebinger Ryan M.; Huentelman Matthew J.; Hulette Christine M.; Hyman Bradley T.; Jayadev Suman; Jin Lee-Way; Johnson Sterling; Karydas Anna; Kaye Jeffrey A.; Kim Ronald; Kowall Neil W.; Kramer Joel H.; LaFerla Frank M.; Lah James J.; Levey Allan I; Li Ge; Lieberman Andrew P.; Lyketsos Constantine G.; Marson Daniel C.; McKee Ann C.; Mesulam Marsel; Mez Jesse; Miller Bruce L.; Miller Carol A.; Moghekar Abhay; Morris John C.; Olichney John M.; Paulson Henry L.; Peskind Elaine; Pierce Aimee; Poon Wayne W.; Puglielli Luigi; Quinn Joseph F.; Raj Ashok; Raskind Murray; Reiman Eric M.; Reisberg Barry; Rissman Robert A.; Roberson Erik D.; Rosen Howard J.; Rosenberg Roger N.; Sadowski Martin; Sager Mark A.; Salmon David P.; Sano Mary; Saykin Andrew J.; Schneider Julie A.; Schneider Lon S.; Seeley William W.; Small Scott; Smith Amanda G.; Stern Robert A.; Swerdlow Russell H.; Tanzi Rudolph E.; Farias Sarah E. Tomaszewski; Trojanowski John Q.; Troncoso Juan C.; Tsuang Debby W.; Van Deerlin Vivianna M.; Van Eldik Linda J.; Vinters Harry V.; Vonsattel Jean Paul; Wang Jen Chyong; Weintraub Sandra; Welsh-Bohmer Kathleen A.; Westaway Shawn; Wingo Thomas S.; Wisniewski Thomas; Wolk David A.; Woltjer Randall L.; Yu Lei; Yu Chang-En; Ikram Kamran; Wolters Frank J.; Adams Perrie; Aguirre Alyssa; Alvarez Lisa; Ayres Gayle; Barber Robert C.; Bertelson John; Brisebois Sarah; Chasse Scott; Culum Munro; Darby Eveleen; DeToledo John C.; Fairchild Thomas J.; Hall James R.; Hart John; Hernandez Michelle; Huebinger Ryan; Johnson Leigh; Johnson Kim; Khaleeq Aisha; Knebl Janice; Lacritz Laura J.; Mains Douglas; Massman Paul; Trung Nguyen; OBryant Sid; Ory Marcia; Palmer Raymond; Pavlik Valory; Paydarfar David; Perez Victoria; Polk Marsha; Quiceno Mary; Reisch Joan S.; Rodriguear Monica; Royall Donald R.; Smith Janet; Stevens Alan; Tilson Jeffrey L.; Wiechmann April; Wilhelmsen Kirk C.; Williams Benjamin; Wilms Henrick; Woon Martin; Adams Larry D.; Carney Regina M.; Celis Katrina; Cuccaro Michael L.; Rajabli Farid; Rogaeva Ekaterina; St George-Hyslop Peter; Korvatska Olena; Raskind Wendy; Dougherty John H.; Gwirtsman Harry E.; Brickman Adam; Manly Jennifer; Reitz Christian; Schupf Nicole; Stern Yaakov;
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中图分类神经病学与精神病学;
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专利

1. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype [J] . Ma Yiyi, Jun Gyungah R., Zhang Xiaoling, JAMA neurology . 2019,第9期

机译：Apoe基因型分层的阿尔茨海默病全外膜序列测序数据分析
2. Data on plasma levels of apolipoprotein E, correlations with lipids and lipoproteins stratified by APOE genotype, and risk of ischemic heart disease [J] . Katrine L. Rasmussen, Anne Tybj?rg-Hansen, B?rge G. Nordestgaard, Data in Brief . 2016,第1期

机译：血浆载脂蛋白E水平，与 APOE 基因型分层的脂质和脂蛋白的相关性以及缺血性心脏病的风险
3. Genetic Evidence for the Involvement of Variants at APOE, BIN1, CR1, and PICALM Loci in Risk of Late-Onset Alzheimer's Disease and Evaluation for Interactions with APOE Genotypes [J] . Gharesouran Jalal, Rezazadeh Maryam, Khorrami Aziz, Journal of Molecular Neuroscience: MN . 2014,第4期

机译：迟发性阿尔茨海默氏病风险中涉及APOE，BIN1，CR1和PICALM基因座变异的遗传证据以及与APOE基因型相互作用的评估
4. Pattern analysis of the interaction of regional amyloid load, cortical thickness and APOE genotype in the progression of Alzheimer's disease [C] . Chunfei Li, Chen Fang, Mercedes Cabrerizo, IEEE International Conference on Bioinformatics and Biomedicine . 2017

机译：阿尔茨海默氏病进展过程中局部淀粉样蛋白负荷，皮层厚度和APOE基因型相互作用的模式分析
5. Differential mortality by APOE epsilon4 genotype: Due to cardiovascular disease, Alzheimer's disease, or both? The Cache County study (Utah). [D] . Hayden, Kathleen M. 2004

机译：APOE epsilon4基因型的死亡率差异：是由于心血管疾病，阿尔茨海默氏病，还是两者兼而有之？凯奇县研究（犹他州）。
6. Classification and Graphical Analysis of Alzheimer’s Disease and Its Prodromal Stage Using Multimodal Features From Structural Diffusion and Functional Neuroimaging Data and the APOE Genotype [O] . Yubraj Gupta, Ji-In Kim, Byeong Chae Kim, 2020

机译：使用结构扩散和功能性神经模仿数据和Apoe基因型的多模式特征对阿尔茨海默病的分类和图形分析及其前期阶段
7. Classification and Graphical Analysis of Alzheimer’s Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype [O] . Yubraj Gupta, Ji-In Kim, Byeong Chae Kim, 2020

机译：使用结构，扩散和功能性神经模仿数据和Apoe基因型的多模式特征对阿尔茨海默病的分类和图形分析及其前期阶段

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Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype

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