e-Article
Long runs of homozygosity are associated with Alzheimer’s disease
Document Type
article
Author
Sonia Moreno-Grau; Maria Victoria Fernández; Itziar de Rojas; Pablo Garcia-González; Isabel Hernández; Fabiana Farias; John P. Budde; Inés Quintela; Laura Madrid; Antonio González-Pérez; Laura Montrreal; Emilio Alarcón-Martín; Montserrat Alegret; Olalla Maroñas; Juan Antonio Pineda; Juan Macías; DEGESCO consortium; Marta Marquié; Sergi Valero; Alba Benaque; Jordi Clarimón; Maria Jesus Bullido; Guillermo García-Ribas; Pau Pástor; Pascual Sánchez-Juan; Victoria Álvarez; Gerard Piñol-Ripoll; Jose María García-Alberca; José Luis Royo; Emilio Franco-Macías; Pablo Mir; Miguel Calero; Miguel Medina; Alberto Rábano; Jesús Ávila; Carmen Antúnez; Luis Miguel Real; Adelina Orellana; Ángel Carracedo; María Eugenia Sáez; Lluís Tárraga; Mercè Boada; Carlos Cruchaga; Agustín Ruiz; for the Alzheimer’s Disease Neuroimaging Initiative
Source
Translational Psychiatry, Vol 11, Iss 1, Pp 1-12 (2021)
Subject
Language
English
ISSN
2158-3188
Abstract
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 AVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; β FROH (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