guest ::
| Home > Articles > Published articles > Long runs of homozygosity are associated with Alzheimer's disease |
| Home > Articles > Published articles > Long runs of homozygosity are associated with Alzheimer's disease |
(Washington University School of Medicine. Hope Center for Neurological Disorders) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Institut Català de Neurociènces Aplicades) (Institut Català de Neurociènces Aplicades) (Washington University School of Medicine. Hope Center for Neurological Disorders) (Washington University School of Medicine. Hope Center for Neurological Disorders) (Universidade de Santiago de Compostela. Grupo de Medicina Xenómica) (Centro Andaluz de Estudios Bioinformáticos-CAEBI) (Institut Català de Neurociènces Aplicades) (Institut Català de Neurociènces Aplicades) (Hospital Universitario Virgen de Valme (Sevilla, Andalusia)) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Institut d'Investigació Biomèdica Sant Pau) (Instituto de Investigación Sanitaria del Hospital Universitario La Paz) (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya)) (Universidad de Cantabria) (Instituto de Investigación Sanitaria del Principado de Asturias) (Instituto Andaluz de Neurociencia) (Instituto de Biomedicina de Sevilla) (Instituto de Salud Carlos III) (Queen Sofia Foundation Alzheimer Center) (Universidad de Málaga. Facultad de Medicina) (Institut Català de Neurociènces Aplicades) (Fundación Pública Galega de Medicina Xenómica) (Centro Andaluz de Estudios Bioinformáticos-CAEBI) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Washington University School of Medicine. Hope Center for Neurological Disorders) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)| Date: | 2021 |
| 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 fine-scale 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 [ β (CI 95%) = 0. 070 (0. 037-0. 104); P = 3. 91 × 10 −5 ; β (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 whole-exome 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. |
| Grants: | Instituto de Salud Carlos III PI13-02434 Instituto de Salud Carlos III PI16-01861 Instituto de Salud Carlos III PI17-01474 Instituto de Salud Carlos III PI19-01301 |
| Note: | Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017). |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Genomics ; Psychiatric disorders |
| Published in: | Translational psychiatry, Vol. 11 (february 2021) , ISSN 2158-3188 |
