ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

被引：57

作者：

Boada, M. ^{[1
,2
]}

Antunez, C. ^{[3
]}

Ramirez-Lorca, R. ^{[4
]}

DeStefano, A. L. ^{[5
,6
]}

Gonzalez-Perez, A. ^{[4
]}

Gayan, J. ^{[4
]}

Lopez-Arrieta, J. ^{[7
]}

Ikram, M. A. ^{[8
,9
]}

Hernandez, I. ^{[1
]}

Marin, J. ^{[3
]}

Galan, J. J. ^{[4
]}

Bis, J. C. ^{[10
]}

Mauleon, A. ^{[1
]}

Rosende-Roca, M. ^{[1
]}

Moreno-Rey, C. ^{[4
]}

Gudnasson, V. ^{[11
]}

Moron, F. J. ^{[4
]}

Velasco, J. ^{[4
]}

Carrasco, J. M. ^{[4
]}

Alegret, M. ^{[1
]}

Espinosa, A. ^{[1
]}

Vinyes, G. ^{[1
]}

Lafuente, A. ^{[1
]}

Vargas, L. ^{[1
]}

Fitzpatrick, A. L. ^{[10
]}

Launer, L. J. ^{[12
]}

Saez, M. E. ^{[4
]}

Vazquez, E. ^{[4
]}

Becker, J. T. ^{[13
,14
,15
]}

Lopez, O. L. ^{[13
]}

Serrano-Rios, M. ^{[16
]}

Tarraga, L. ^{[1
]}

van Duijn, C. M. ^{[8
,9
]}

Real, L. M. ^{[4
]}

Seshadri, S. ^{[5
,6
,17
]}

Ruiz, A. ^{[1
,4
]}

机构：

[1] Fdn ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 08029, Spain

[2] Univ Autonoma Barcelona VHIR UAB, Hosp Univ Vall dHebron Inst Recerca, E-08193 Barcelona, Spain

[3] Univ Hosp Virgen de la Arrixaca, Dementia Unit, Murcia, Spain

[4] Neocodex, Dept Struct Genom, Seville, Spain

[5] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[6] Boston Univ, Sch Med, Dept Biostat, Boston, MA USA

[7] Univ Hosp La Paz Cantoblanco, Memory Unit, Madrid, Spain

[8] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[9] Netherlands Consortium Hlth Aging, Leiden, Netherlands

[10] Univ Washington, Dept Med, Seattle, WA USA

[11] Kopavogur Univ Iceland, Icelandic Heart Assoc, Kopavogur, Iceland

[12] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Washington, DC USA

[13] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, Pittsburgh, PA USA

[14] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat, Pittsburgh, PA USA

[15] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychol, Pittsburgh, PA USA

[16] Hosp Clin San Carlos, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain

[17] NHLBI, Framingham Heart Study, Framingham, MA USA

来源：

MOLECULAR PSYCHIATRY | 2014年 / 19卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; genomics; GWAS; molecular epidemiology; SNP; GENOME-WIDE ASSOCIATION; LATE-ONSET ALZHEIMERS; IDENTIFIES VARIANTS; COMMON VARIANTS; GENE; VISUALIZATION; POPULATION; EXPRESSION; CARRIERS; MODIFY;

D O I：

10.1038/mp.2013.86

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 x 10(-6) were genotyped in an independent Stage III sample (the Fundacio ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H + transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)= 1.58, P= 2.6 X 10(-7) in discovery and OR 1.43, P= 0.004 in Fundacio ACE data set; combined OR= 1.53, P= 4.7 X 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

引用

页码：682 / 687

页数：6

共 43 条

[1]

GRR: graphical representation of relationship errors [J].

Abecasis, GR ;

Cherny, SS ;

Cookson, WOC ;

Cardon, LR .

BIOINFORMATICS, 2001, 17 (08) :742-743

[2]

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease [J].

Antunez, Carmen ;

Boada, Merce ;

Gonzalez-Perez, Antonio ;

Gayan, Javier ;

Ramirez-Lorca, Reposo ;

Marin, Juan ;

Hernandez, Isabel ;

Moreno-Rey, Concha ;

Jesus Moron, Francisco ;

Lopez-Arrieta, Jesus ;

Mauleon, Ana ;

Rosende-Roca, Maitee ;

Noguera-Perea, Fuensanta ;

Legaz-Garcia, Agustina ;

Vivancos-Moreau, Laura ;

Velasco, Juan ;

Miguel Carrasco, Jose ;

Alegret, Montserrat ;

Antequera-Torres, Martirio ;

Manzanares, Salvadora ;

Romo, Alejandro ;

Blanca, Irene ;

Ruiz, Susana ;

Espinosa, Anna ;

Castano, Sandra ;

Garcia, Blanca ;

Martinez-Herrada, Begona ;

Vinyes, Georgina ;

Lafuente, Asuncion ;

Becker, James T. ;

Jorge Galan, Jose ;

Serrano-Rios, Manuel ;

Vazquez, Enrique ;

Tarraga, Lluis ;

Eugenia Saez, Maria ;

Lopez, Oscar L. ;

Miguel Real, Luis ;

Ruiz, Agustin .

GENOME MEDICINE, 2011, 3

[3]

Antunez Carmen, 2011, Alzheimers Dement, V7, pe124, DOI 10.1016/j.jalz.2011.05.2412

[4]

Alzheimer's disease [J].

Ballard, Clive ;

Gauthier, Serge ;

Corbett, Anne ;

Brayne, Carol ;

Aarsland, Dag ;

Jones, Emma .

LANCET, 2011, 377 (9770) :1019-1031

[5]

Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[6]

KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases [J].

Bayon, Yolanda ;

Trinidad, Antonio G. ;

de la Puerta, Maria L. ;

Rodriguez, Maria del Carmen ;

Bogetz, Jori ;

Rojas, Ana ;

De Pereda, Jose M. ;

Rahmouni, Souad ;

Williams, Scott ;

Matsuzawa, Shu-ichi ;

Reed, John C. ;

Crespo, Mariano Sanchez ;

Mustelin, Tomas ;

Alolnso, Andres .

FEBS JOURNAL, 2008, 275 (15) :3900-3910

[7]

GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].

CORDER, EH ;

SAUNDERS, AM ;

STRITTMATTER, WJ ;

SCHMECHEL, DE ;

GASKELL, PC ;

SMALL, GW ;

ROSES, AD ;

HAINES, JL ;

PERICAKVANCE, MA .

SCIENCE, 1993, 261 (5123) :921-923

[8]

Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions [J].

Ding, Xiao-Feng ;

Luo, Chang ;

Ren, Kai-Qun ;

Zhang, Jing ;

Zhou, Jian-Lin ;

Hu, Xiang ;

Liu, Ru-Shi ;

Wang, Yan ;

Gao, Xiang ;

Zhang, Jian .

DNA AND CELL BIOLOGY, 2008, 27 (05) :257-265

[9]

Genetic Structure of the Spanish Population [J].

Gayan, Javier ;

Galan, Jose J. ;

Gonzalez-Perez, Antonio ;

Eugenia Saez, Maria ;

Teresa Martinez-Larrad, Maria ;

Zabena, Carina ;

Carmen Rivero, M. ;

Salinas, Ana ;

Ramirez-Lorca, Reposo ;

Moron, Francisco J. ;

Luis Royo, Jose ;

Moreno-Rey, Concha ;

Velasco, Juan ;

Carrasco, Jose M. ;

Molero, Eva ;

Ochoa, Carolina ;

Dolores Ochoa, Maria ;

Gutierrez, Marta ;

Reina, Mercedes ;

Pascual, Rocio ;

Romo-Astorga, Alejandro ;

Luis Susillo-Gonzalez, Juan ;

Vazquez, Enrique ;

Real, Luis M. ;

Ruiz, Agustin ;

Serrano-Rios, Manuel .

BMC GENOMICS, 2010, 11

[10]

Solution Structure of the Catalytic Domain of the Mitochondrial Protein ICT1 That Is Essential for Cell Vitality [J].

Handa, Yoshihiro ;

Hikawa, Yusuke ;

Tochio, Naoya ;

Kogure, Hiroyuki ;

Inoue, Makoto ;

Koshiba, Seizo ;

Guentert, Peter ;

Inoue, Yusuke ;

Kigawa, Takanori ;

Yokoyama, Shigeyuki ;

Nameki, Nobukazu .

JOURNAL OF MOLECULAR BIOLOGY, 2010, 404 (02) :260-273

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