dc.creator | Moreno-Grau, Sonia | es |
dc.creator | Fernández, María Victoria | es |
dc.creator | de Rojas, Itziar | es |
dc.creator | García-González, Pablo | es |
dc.creator | Hernández, Isabel | es |
dc.creator | Farias, Fabiana | es |
dc.creator | Pineda Vergara, Juan Antonio | es |
dc.creator | Macías Sánchez, Juan | es |
dc.creator | Mir Rivera, Pablo | es |
dc.creator | Periñán Tocino, María Teresa | es |
dc.date.accessioned | 2022-10-03T15:40:28Z | |
dc.date.available | 2022-10-03T15:40:28Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Moreno-Grau, S., Fernández, M.V., de Rojas, I., García-González, P., Hernández, I., Farias, F.,...,Periñán Tocino, M.T. (2021). Long runs of homozygosity are associated with Alzheimer’s disease. Translational Psychiatry, 11 (1). https://doi.org/10.1038/s41398-020-01145-1. | |
dc.identifier.issn | 2158-3188 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137574 | |
dc.description.abstract | Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of
inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD);
however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a finescale
ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We
detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P =
3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly
overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk
was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value =
9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a
homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in wholeexome
sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which
has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive
variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting
that recessive effects may explain a proportion of AD heritability. | es |
dc.description.sponsorship | Consejería de Salud de la Junta de Andalucía PI-0001/2017 | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | Translational Psychiatry, 11 (1). | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Alzheimer’s disease | es |
dc.title | Long runs of homozygosity are associated with Alzheimer’s disease | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.projectID | PI-0001/2017 | es |
dc.relation.publisherversion | https://www.nature.com/articles/s41398-020-01145-1 | es |
dc.identifier.doi | 10.1038/s41398-020-01145-1 | es |
dc.journaltitle | Translational Psychiatry | es |
dc.publication.volumen | 11 | es |
dc.publication.issue | 1 | es |