Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease

被引：20

作者：

Barral, Sandra ^{[1
,2
,3
,4
]}

Cheng, Rong ^{[1
,2
]}

Reitz, Christiane ^{[1
,2
,3
,4
,5
]}

Vardarajan, Badri ^{[1
,2
,3
,4
]}

Lee, Joseph ^{[1
,2
,5
]}

Kunkle, Brian ^{[7
]}

Beecham, Gary ^{[7
]}

Cantwell, Laura S. ^{[8
]}

Pericak-Vance, Margaret A. ^{[7
,9
]}

Farrer, Lindsay A. ^{[10
,11
,12
,13
,14
]}

Haines, Jonathan L. ^{[15
]}

Goate, Alison M. ^{[16
]}

Foroud, Tatiana ^{[17
]}

Boerwinkle, Eric ^{[4
,6
,18
]}

Schellenberg, Gerard D. ^{[8
]}

Mayeux, Richard ^{[1
,2
,3
,4
,5
]}

机构：

[1] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA

[2] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, New York, NY USA

[3] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA

[4] New York Presbyterian Hosp, New York, NY USA

[5] Columbia Univ, Sch Publ Hlth, Dept Epidemiol, New York, NY USA

[6] Univ Texas Sch Publ Hlth Houston, Dept Epidemiol Human Genet & Environm Sci EHGES, Houston, TX USA

[7] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA

[8] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[9] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA

[10] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[11] Boston Univ, Sch Med & Publ Hlth, Dept Med Biomed Genet, Boston, MA 02215 USA

[12] Boston Univ, Sch Med & Publ Hlth, Dept Neurol, Boston, MA 02215 USA

[13] Boston Univ, Sch Med & Publ Hlth, Dept Ophthalmol, Boston, MA 02215 USA

[14] Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA

[15] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA

[16] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[17] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[18] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA

来源：

ALZHEIMERS & DEMENTIA | 2015年 / 11卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Caribbean Hispanic families; Late-onset Alzheimer's disease; Linkage analysis; Joint linkage and association; MISSENSE MUTATIONS; GENE; DIAGNOSIS; VARIANTS; ZINC; IDENTIFICATION; CONFIRMATION; METAANALYSIS; POPULATION; SIMULATION;

D O I：

10.1016/j.jalz.2015.07.487

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: We performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants. Methods: We selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association. Results: We identified 26 regions linked to LOAD(HLOD >= 3.6). We validated 13 of the regions (HLOD >= 2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax = 4.7, P-joint = 6.6 x 10(-6)), a locus located similar to 2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLODmax = 4.9, P-joint = 1.2 x 10(-5)), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6). Discussion: Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

引用

页码：1397 / 1406

页数：10

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