Search for the Alzheimer's Gene on Chromosome 10

寻找 10 号染色体上的阿尔茨海默病基因

基本信息

  • 批准号:
    7762196
  • 负责人:
  • 金额:
    $ 74.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-02-15 至 2014-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by principal investigator): Late-onset Alzheimer's disease (LOAD) is a complex and multifactorial disease with the possible involvement of several genes. Apolipoprotein E (APOE), especially the APOE*4 allele, has been established as a strong susceptibility marker that accounts for 20-29 percent of the risk in LOAD. In addition to the disease risk, age-at-onset (AAO) of AD is also genetically controlled and the APOE gene accounts for <10 percent of the variation in AAO. This emphasizes the involvement of other genetic and/or environmental factors, which alone or in conjunction with APOE*4, can modify the risk or AAO of AD. Recently, genomewide linkage on LOAD have provided evidence for the existence of multiple putative genes for AD on several chromosomes with the strongest evidence on chromosomes 9, 10 and 12. With the construction of a high-density map of single nucleotide polymorphisms (SNPs) in the human genome, it is now possible to use the population-based association studies approach to identify the putative AD risk genes. A broad linkage peak encompassing >65 Mb region between chromosome 10q11 (at 50 Mb) and 10q25 (at 116 Mb) that influences both AD risk and AAO has been suggested. As part of our preliminary data we have screened 21 SNPs in 13 known biological candidate genes located under this broad >65 Mb linkage region in our large case-control cohort and identified suggestive significant associations with SNPs located in the choline acetyltransferase (CHAT) gene at 50.5 Mb on 10q11 and urokinase-type plasminogen activator (PLAU) gene at 75.3 Mb on 10q22 and thus our association findings are compliment to the reported linkage studies. This provides a strong rationale to comprehensively examine this linkage region by high-powered association studies to identify the chromosome 10 AD gene. The primary goal of this application is to comprehensively examine the ~65 Mb region between 10q11 and 10q25 first screening extensive panels of linkage disequilibrium (LD)-tagging SNPs in a first stage discovery sample to identify significant SNPs (Aim 1) and then confirm the significant findings in a second stage replication sample (Aim 2). The genes harboring confirmed significant SNPs in both stage analyses will then be comprehensively screened as part of Aim 3 to identify the putative functional SNPs. PUBLIC HEALTH RELEVANCE Alzheimer's disease (AD) is a major public health problem in the U.S. because it has a long clinical course, but there is no cure. Although AD has a strong genetic basis, only a small fraction of the genetic contribution has been discovered. Genome-wide linkage studies have implicated several chromosomal regions that might harbor multiple genes for AD. This study is focused on identifying the AD gene on chromosome 10 by using a large case-control sample in the discovery sample and a family-based sample in the replication sample.
描述(由主要研究者提供):迟发性阿尔茨海默病(LOAD)是一种复杂的多因素疾病,可能涉及几个基因。载脂蛋白E(APOE),特别是APOE*4等位基因,已被确定为一个强的易感性标志物,占LOAD风险的20- 29%。除了疾病风险外,AD的发病年龄(AAO)也受到遗传控制,APOE基因占AAO变异的<10%。这强调了其他遗传和/或环境因素的参与,这些因素单独或与APOE*4一起可以改变AD的风险或AAO。最近,LOAD上的全基因组连锁提供了证据,表明在几条染色体上存在多个AD推定基因,其中在染色体9、10和12上的证据最强。随着人类基因组单核苷酸多态性(SNPs)高密度图谱的构建,现在可以使用基于人群的关联研究方法来识别推定的AD风险基因。在染色体10 q11(50 Mb)和10 q25(116 Mb)之间存在一个包含>65 Mb区域的广泛连锁峰,该连锁峰影响AD风险和AAO。作为我们的初步数据的一部分,我们在我们的大型病例对照队列中筛选了13个已知生物学候选基因中的21个SNP,这些基因位于这个>65 Mb的广泛连锁区域,并确定了与位于10 q11上50.5 Mb的胆碱乙酰转移酶(CHAT)基因和尿激酶型纤溶酶原激活剂(PLAU)中的SNP的显著关联。基因位于10 q22上的75.3 Mb,因此我们的关联发现是对已报道的连锁研究的补充。这提供了一个强有力的理由,全面检查这个连锁区域的高功率关联研究,以确定染色体10 AD基因。本申请的主要目标是全面检查10 q11和10 q25之间的~65 Mb区域,在第一阶段发现样本中首次筛选广泛的连锁不平衡(LD)标记SNP组,以鉴定显著的SNP(Aim 1),然后在第二阶段复制样本中确认显著的发现(Aim 2)。然后,作为目标3的一部分,对在两个阶段分析中确认具有显著SNP的基因进行全面筛选,以鉴定推定的功能性SNP。阿尔茨海默氏病(AD)是美国的一个主要公共卫生问题,因为它有很长的临床病程,但没有治愈方法。虽然AD具有很强的遗传基础,但仅发现了一小部分遗传贡献。全基因组连锁研究已经涉及到几个染色体区域,可能窝藏多个基因的AD。本研究的重点是通过在发现样本中使用大的病例对照样本和在复制样本中使用基于家族的样本来鉴定10号染色体上的AD基因。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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M. Ilyas Kamboh其他文献

Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
  • DOI:
    10.1186/s13195-025-01803-w
  • 发表时间:
    2025-07-25
  • 期刊:
  • 影响因子:
    7.600
  • 作者:
    Menayit Tamrat Dresse;Pamela C. L. Ferreira;Akshay Prasadan;Jihui L. Diaz;Xuemei Zeng;Bruna Bellaver;Guilherme Povala;Victor L. Villemagne;M. Ilyas Kamboh;Ann D. Cohen;Tharick A. Pascoal;Mary Ganguli;Beth E. Snitz;C. Elizabeth Shaaban;Thomas K. Karikari
  • 通讯作者:
    Thomas K. Karikari
Search for the elusive haplotype of the APOE polymorphism associated with Alzheimer’s disease
寻找与阿尔茨海默病相关的载脂蛋白 E 多态性的难以捉摸的单倍型
  • DOI:
    10.1038/s41598-025-01263-0
  • 发表时间:
    2025-05-15
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Asma Naseer Cheema;Kang-Hsien Fan;Elizabeth Lawrence;Narges Zafari;Ruyu Shi;Muhammad Muaaz Aslam;Vibha Acharya;Alayna Jean Holderman;Annie Bedison;Eleanor Feingold;M. Ilyas Kamboh
  • 通讯作者:
    M. Ilyas Kamboh
A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism
与 A4POE*4 相关的阿尔茨海默病风险会被α1-抗胰凝乳蛋白酶多态性所修饰
  • DOI:
    10.1038/ng0895-486
  • 发表时间:
    1995-08-01
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    M. Ilyas Kamboh;Dharambir K. Sanghera;Robert E. Ferrell;Steven T. DeKosky
  • 通讯作者:
    Steven T. DeKosky
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer’s disease
  • DOI:
    10.1186/s13059-025-03564-z
  • 发表时间:
    2025-07-17
  • 期刊:
  • 影响因子:
    9.400
  • 作者:
    Farid Rajabli;Penelope Benchek;Giuseppe Tosto;Nicholas Kushch;Jin Sha;Katrina Bazemore;Congcong Zhu;Wan-Ping Lee;Jacob Haut;Kara L. Hamilton-Nelson;Nicholas R. Wheeler;Yi Zhao;John J. Farrell;Michelle A. Grunin;Yuk Yee Leung;Pavel P. Kuksa;Donghe Li;Eder Lucio da Fonseca;Jesse B. Mez;Ellen L. Palmer;Jagan Pillai;Richard M. Sherva;Yeunjoo E. Song;Xiaoling Zhang;Takeshi Ikeuchi;Taha Iqbal;Omkar Pathak;Otto Valladares;Dolly Reyes-Dumeyer;Amanda B. Kuzma;Erin Abner;Larry D. Adams;Perrie M. Adams;Alyssa Aguirre;Marilyn S. Albert;Roger L. Albin;Mariet Allen;Lisa Alvarez;Liana G. Apostolova;Steven E. Arnold;Sanjay Asthana;Craig S. Atwood;Sanford Auerbach;Gayle Ayres;Clinton T. Baldwin;Robert C. Barber;Lisa L. Barnes;Sandra Barral;Thomas G. Beach;James T. Becker;Gary W. Beecham;Duane Beekly;Bruno A. Benitez;David Bennett;John Bertelson;Thomas D. Bird;Deborah Blacker;Bradley F. Boeve;James D. Bowen;Adam Boxer;James Brewer;James R. Burke;Jeffrey M. Burns;Joseph D. Buxbaum;Nigel J. Cairns;Laura B. Cantwell;Chuanhai Cao;Christopher S. Carlson;Cynthia M. Carlsson;Regina M. Carney;Minerva M. Carrasquillo;Scott Chasse;Marie-Francoise Chesselet;Nathaniel A. Chin;Helena C. Chui;Jaeyoon Chung;Suzanne Craft;Paul K. Crane;David H. Cribbs;Elizabeth A. Crocco;Carlos Cruchaga;Michael L. Cuccaro;Munro Cullum;Eveleen Darby;Barbara Davis;Philip L. De Jager;Charles DeCarli;John DeToledo;Malcolm Dick;Dennis W. Dickson;Beth A. Dombroski;Rachelle S. Doody;Ranjan Duara;NIlüfer Ertekin-Taner;Denis A. Evans;Kelley M. Faber;Thomas J. Fairchild;Kenneth B. Fallon;David W. Fardo;Martin R. Farlow;Victoria Fernandez-Hernandez;Steven Ferris;Robert P. Friedland;Tatiana M. Foroud;Matthew P. Frosch;Brian Fulton-Howard;Douglas R. Galasko;Adriana Gamboa;Marla Gearing;Daniel H. Geschwind;Bernardino Ghetti;John R. Gilbert;Rodney C.P. Go;Alison M. Goate;Thomas J. Grabowski;Neill R. Graff-Radford;Robert C. Green;John H. Growdon;Hakon Hakonarson;James Hall;Ronald L. Hamilton;Oscar Harari;John Hardy;Lindy E. Harrell;Elizabeth Head;Victor W. Henderson;Michelle Hernandez;Timothy Hohman;Lawrence S. Honig;Ryan M. Huebinger;Matthew J. Huentelman;Christine M. Hulette;Bradley T. Hyman;Linda S. Hynan;Laura Ibanez;Gail P. Jarvik;Suman Jayadev;Lee-Way Jin;Kim Johnson;Leigh Johnson;M. Ilyas Kamboh;Anna M. Karydas;Mindy J. Katz;John S. Kauwe;Jeffrey A. Kaye;C. Dirk Keene;Aisha Khaleeq;Masataka Kikuchi;Ronald Kim;Janice Knebl;Neil W. Kowall;Joel H. Kramer;Walter A. Kukull;Frank M. LaFerla;James J. Lah;Eric B. Larson;Alan Lerner;James B. Leverenz;Allan I. Levey;Andrew P. Lieberman;Richard B. Lipton;Mark Logue;Oscar L. Lopez;Kathryn L. Lunetta;Constantine G. Lyketsos;Douglas Mains;Flanagan E. Margaret;Daniel C. Marson;Eden RR. Martin;Frank Martiniuk;Deborah C. Mash;Eliezer Masliah;Paul Massman;Arjun Masurkar;Wayne C. McCormick;Susan M. McCurry;Andrew N. McDavid;Stefan McDonough;Ann C. McKee;Marsel Mesulam;Bruce L. Miller;Carol A. Miller;Joshua W. Miller;Thomas J. Montine;Edwin S. Monuki;John C. Morris;Shubhabrata Mukherjee;Amanda J. Myers;Trung Nguyen;Thomas Obisesan;Sid O’Bryant;John M. Olichney;Marcia Ory;Raymond Palmer;Joseph E. Parisi;Henry L. Paulson;Valory Pavlik;David Paydarfar;Victoria Perez;Elaine Peskind;Ronald C. Petersen;Helen Petrovitch;Aimee Pierce;Marsha Polk;Wayne W. Poon;Huntington Potter;Liming Qu;Mary Quiceno;Joseph F. Quinn;Ashok Raj;Murray Raskind;Eric M. Reiman;Barry Reisberg;Joan S. Reisch;John M. Ringman;Erik D. Roberson;Monica Rodriguear;Ekaterina Rogaeva;Howard J. Rosen;Roger N. Rosenberg;Donald R. Royall;Marwan Sabbagh;A. Dessa Sadovnick;Mark A. Sager;Mary Sano;Andrew J. Saykin;Julie A. Schneider;Lon S. Schneider;William W. Seeley;Susan H. Slifer;Scott Small;Amanda G. Smith;Janet P. Smith;Joshua A. Sonnen;Salvatore Spina;Peter St George-Hyslop;Takiyah D. Starks;Robert A. Stern;Alan B. Stevens;Stephen M. Strittmatter;David Sultzer;Russell H. Swerdlow;Rudolph E. Tanzi;Jeffrey L. Tilson;John Q. Trojanowski;Juan C. Troncoso;Magda Tsolaki;Debby W. Tsuang;Vivianna M. Van Deerlin;Linda J. van Eldik;Jeffery M. Vance;Badri N. Vardarajan;Robert Vassar;Harry V. Vinters;Jean-Paul Vonsattel;Sandra Weintraub;Kathleen A. Welsh-Bohmer;Patrice L. Whitehead;Ellen M. Wijsman;Kirk C. Wilhelmsen;Benjamin Williams;Jennifer Williamson;Henrik Wilms;Thomas S. Wingo;Thomas Wisniewski;Randall L. Woltjer;Martin Woon;Clinton B. Wright;Chuang-Kuo Wu;Steven G. Younkin;Chang-En Yu;Lei Yu;Xiongwei Zhu;Brian W. Kunkle;William S. Bush;Akinori Miyashita;Goldie S. Byrd;Li-San Wang;Lindsay A. Farrer;Jonathan L. Haines;Richard Mayeux;Margaret A. Pericak-Vance;Gerard D. Schellenberg;Gyungah R. Jun;Christiane Reitz;Adam C. Naj
  • 通讯作者:
    Adam C. Naj
A Brief Synopsis on the Genetics of Alzheimer’s Disease
  • DOI:
    10.1007/s40142-018-0155-8
  • 发表时间:
    2018-10-30
  • 期刊:
  • 影响因子:
    1.300
  • 作者:
    M. Ilyas Kamboh
  • 通讯作者:
    M. Ilyas Kamboh

M. Ilyas Kamboh的其他文献

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{{ truncateString('M. Ilyas Kamboh', 18)}}的其他基金

Biomarker and Neurogenetics Core
生物标志物和神经遗传学核心
  • 批准号:
    10590714
  • 财政年份:
    2020
  • 资助金额:
    $ 74.83万
  • 项目类别:
Biomarker and Neurogenetics Core
生物标志物和神经遗传学核心
  • 批准号:
    10410387
  • 财政年份:
    2020
  • 资助金额:
    $ 74.83万
  • 项目类别:
Biomarker and Neurogenetics Core
生物标志物和神经遗传学核心
  • 批准号:
    10161692
  • 财政年份:
    2020
  • 资助金额:
    $ 74.83万
  • 项目类别:
Search for the Alzheimers Genes
寻找阿尔茨海默病基因
  • 批准号:
    9190589
  • 财政年份:
    2016
  • 资助金额:
    $ 74.83万
  • 项目类别:
Deep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's Disease
晚发性阿尔茨海默病候选基因区域的深度重测序
  • 批准号:
    8435118
  • 财政年份:
    2012
  • 资助金额:
    $ 74.83万
  • 项目类别:
Deep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's Disease
晚发性阿尔茨海默病候选基因区域的深度重测序
  • 批准号:
    8721824
  • 财政年份:
    2012
  • 资助金额:
    $ 74.83万
  • 项目类别:
Deep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's Disease
晚发性阿尔茨海默病候选基因区域的深度重测序
  • 批准号:
    8554751
  • 财政年份:
    2012
  • 资助金额:
    $ 74.83万
  • 项目类别:
Deep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's Disease
晚发性阿尔茨海默病候选基因区域的深度重测序
  • 批准号:
    9094395
  • 财政年份:
    2012
  • 资助金额:
    $ 74.83万
  • 项目类别:
Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    8217122
  • 财政年份:
    2010
  • 资助金额:
    $ 74.83万
  • 项目类别:
Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    8423754
  • 财政年份:
    2010
  • 资助金额:
    $ 74.83万
  • 项目类别:

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项目 1 - 发挥功能的基因:因果基因及其在心肌细胞和心房生理学中的作用
  • 批准号:
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  • 批准号:
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Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    8217122
  • 财政年份:
    2010
  • 资助金额:
    $ 74.83万
  • 项目类别:
Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    8423754
  • 财政年份:
    2010
  • 资助金额:
    $ 74.83万
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Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    8030415
  • 财政年份:
    2010
  • 资助金额:
    $ 74.83万
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Search for the Alzheimer's Gene on Chromosome 10
寻找 10 号染色体上的阿尔茨海默病基因
  • 批准号:
    7577259
  • 财政年份:
    2009
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    $ 74.83万
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Investigating the Role of Genomic Copy Number Variation in Risk for Schizophrenia
研究基因组拷贝数变异在精神分裂症风险中的作用
  • 批准号:
    7417428
  • 财政年份:
    2007
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Investigating the Role of Genomic Copy Number Variation in Risk for Schizophrenia
研究基因组拷贝数变异在精神分裂症风险中的作用
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    $ 74.83万
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THE GENETICS OF NICOTINE DEPENDENCE
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    7600993
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