Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

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Lambert, J-C (author)

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Article/chapterEnglish2013

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2012-03-20
Springer Science and Business Media LLC,2013
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LIBRIS-ID:oai:DiVA.org:uu-198612
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-198612URI
https://doi.org/10.1038/mp.2012.14DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-89578URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:126412333URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Correction in: Molecular Psychiatry (2013) 18, 521–521doi:10.1038/mp.2012.75
AuthorCount:74;
Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.

Subject headings and genre

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Psykiatri hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Psychiatry hsv//eng
Alzheimer
amyloid
FRMD4A
GWAS
plasma

Added entries (persons, corporate bodies, meetings, titles ...)

Grenier-Boley, B. (author)
Harold, D. (author)
Zelenika, D. (author)
Chouraki, V. (author)
Kamatani, Y. (author)
Sleegers, K. (author)
Ikram, M. A. (author)
Hiltunen, M. (author)
Reitz, C. (author)
Mateo, I. (author)
Feulner, T. (author)
Bullido, M. (author)
Galimberti, D. (author)
Concari, L. (author)
Alvarez, V. (author)
Sims, R. (author)
Gerrish, A. (author)
Chapman, J. (author)
Deniz-Naranjo, C. (author)
Solfrizzi, V. (author)
Sorbi, S. (author)
Arosio, B. (author)
Spalletta, G. (author)
Siciliano, G. (author)
Epelbaum, J. (author)
Hannequin, D. (author)
Dartigues, J-F (author)
Tzourio, C. (author)
Berr, C. (author)
Schrijvers, E. M. C. (author)
Rogers, R. (author)
Tosto, G. (author)
Pasquier, F. (author)
Bettens, K. (author)
Van Cauwenberghe, C. (author)
Fratiglioni, L.Karolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI) (author)
Graff, C.Karolinska Institutet (author)
Delepine, M. (author)
Ferri, R. (author)
Reynolds, C. A. (author)
Lannfelt, LarsUppsala universitet,Geriatrik,molekylär geriatrik/ rudbecklaboratoriet(Swepub:uu)lalan021 (author)
Ingelsson, MartinUppsala universitet,Geriatrik,molekylär geriatrik/ rudbecklaboratoriet(Swepub:uu)maing121 (author)
Prince, J. A.Karolinska Institutet (author)
Chillotti, C. (author)
Pilotto, A. (author)
Seripa, D. (author)
Boland, A. (author)
Mancuso, M. (author)
Bossu, P. (author)
Annoni, G. (author)
Nacmias, B. (author)
Bosco, P. (author)
Panza, F. (author)
Sanchez-Garcia, F. (author)
Del Zompo, M. (author)
Coto, E. (author)
Owen, M. (author)
O'Donovan, M. (author)
Valdivieso, F. (author)
Caffara, P. (author)
Scarpini, E. (author)
Combarros, O. (author)
Buee, L. (author)
Campion, D. (author)
Soininen, H. (author)
Breteler, M. (author)
Riemenschneider, M. (author)
Van Broeckhoven, C. (author)
Alperovitch, A. (author)
Lathrop, M. (author)
Tregouet, D-A (author)
Williams, J. (author)
Amouyel, P. (author)
Stockholms universitetCentrum för forskning om äldre och åldrande (ARC), (tills m KI) (creator_code:org_t)

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In:Molecular Psychiatry: Springer Science and Business Media LLC18:4, s. 461-4701359-41841476-5578

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By the author/editor: Lambert, J-C; Grenier-Boley, B ...; Harold, D.; Zelenika, D.; Chouraki, V.; Kamatani, Y.; show more...; Sleegers, K.; Ikram, M. A.; Hiltunen, M.; Reitz, C.; Mateo, I.; Feulner, T.; Bullido, M.; Galimberti, D.; Concari, L.; Alvarez, V.; Sims, R.; Gerrish, A.; Chapman, J.; Deniz-Naranjo, C ...; Solfrizzi, V.; Sorbi, S.; Arosio, B.; Spalletta, G.; Siciliano, G.; Epelbaum, J.; Hannequin, D.; Dartigues, J-F; Tzourio, C.; Berr, C.; Schrijvers, E. M ...; Rogers, R.; Tosto, G.; Pasquier, F.; Bettens, K.; Van Cauwenberghe ...; Fratiglioni, L.; Graff, C.; Delepine, M.; Ferri, R.; Reynolds, C. A.; Lannfelt, Lars; Ingelsson, Marti ...; Prince, J. A.; Chillotti, C.; Pilotto, A.; Seripa, D.; Boland, A.; Mancuso, M.; Bossu, P.; Annoni, G.; Nacmias, B.; Bosco, P.; Panza, F.; Sanchez-Garcia, ...; Del Zompo, M.; Coto, E.; Owen, M.; O'Donovan, M.; Valdivieso, F.; Caffara, P.; Scarpini, E.; Combarros, O.; Buee, L.; Campion, D.; Soininen, H.; Breteler, M.; Riemenschneider, ...; Van Broeckhoven, ...; Alperovitch, A.; Lathrop, M.; Tregouet, D-A; Williams, J.; Amouyel, P.; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Psychiatry

Articles in the publication: Molecular Psychi ...

By the university: Uppsala University; Stockholm University; Karolinska Institutet

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