Follow-up of loci from the International Genomics of Alzheimer’s Disease Project identifies TRIP4 as a novel susceptibility gene
Open accessAbstract
To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 × 10(-)(9)).
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Additional genetic risk factors for AD hint at a plurality of mechanisms through which AD is developed.
“Besides APOE, additional genetic risk factors for AD, such as those identified by linkage analysis and GWAS in the IGAP study, hint at a plurality of mechanisms through which AD is developed (6, 44, 45).”
From Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets (2021) · cites this paper as [44]
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References 19 · Cited by 97
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- Tan ZS Beiser A Vasan RS Au R Auerbach S Kiel DP Thyroid function and the risk of Alzheimer disease: the Framingham Study Arch Intern Med 2008 168 1514 1520 18663163 PMC2694610
- Authors
- Ruiz, A., Heilmann, S., Becker, T., Hernández, I., Wagner, H., Thelen, M., Mauleón, A., Rosende-Roca, M., Bellenguez, C., Bis, J. C., Harold, D., Gerrish, A., Sims, R., Sotolongo-Grau, O., Espinosa, A., Alegret, M., Arrieta, J. L., Lacour, A., Leber, M., Becker, J., Lafuente, A., Ruiz, S., Vargas, L., Rodríguez, O., Ortega, G., Dominguez, M.-A., IGAP, Mayeux, R., Haines, J. L., Pericak-Vance, M. A., Farrer, L. A., Schellenberg, G. D., Chouraki, V, Launer, L. J., van Duijn, C., Seshadri, S., Antúnez, C., Breteler, M. M., Serrano-Ríos, M., Jessen, F., Tárraga, L., Nöthen, M. M., Maier, W., Boada, M., & Ramírez, A.
- Affiliations
- Fundació ACE (ES)
- University of Bonn (DE)
- Inserm (FR)
- University of Washington (US)
- Cardiff University (GB)
- Hospital Universitario La Paz (ES)
- German Center for Neurodegenerative Diseases (DE)
- Columbia University Irving Medical Center (US)
- Vanderbilt University (US)
- University of Miami (US)
- Boston University (US)
- National Institutes of Health (US)
- Universitat Autònoma de Barcelona (ES)
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2014-02-04
- Volume
- 4
- Issue
- 2
- Pages
- e358-e358
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3944635
- OpenAlex
- W2088446425
- Cited by
- 97
- References
- 19
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 11 · 2020: 5 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 20 · 2015: 8 · 2014: 1
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung (01GI0102, 01GI0715, 01GI0429, 01GI0434, 01GI0423, 01GI0422, 01GI0712, 01ET1006B, 01GI0711, 01GI0716, 01GI0431, 01GI0713, 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B, 01GI0420, 01GI0710, 01GI0714, 01GI0433, 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716)
- Ministerio de Economía y Competitividad
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- National Institutes of Health
- Instituto de Salud Carlos III (PI13/02434)
- National Institute on Aging (U01AG049505, U01AG032984, AG033193, R01AG041797, P30AG013846, R01AG033193, R01AG008122, U24AG056270, U24AG021886)
- National Human Genome Research Institute (U01HG006375)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, genetic susceptibility, INPP5D, MEF2C, FERMT2, single nucleotide polymorphisms, genetic association, replication study, Spanish population
- MeSH terms
- Alzheimer Disease, Follow-Up Studies, Humans, Spain, Transcription Factors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci
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