F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease

Annals of Clinical and Translational Neurology
Giuseppe TostoR Mayeux

Abstract

In the context of late-onset Alzheimer's disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD. About 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis. Significant loci were further tested in the expanded cohort that also included related family members (n = 5300). Two AD-like transgenic mice models (J20 and rTg4510) were used to study gene expression. Independent data sets of non-Hispanic Whites and African Americans were used to further validate findings, along with publicly available brain expression data sets. A novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case-control cohort (odd ratio [OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts (OR = 0.63, P = 4.7E-08). Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates. Publicly available microarra...Continue Reading

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Citations

Dec 22, 2016·Human Heredity·Gaël NicolasDominique Campion
May 17, 2017·Journal of Alzheimer's Disease : JAD·Jin-Bao ZhuJin-Tai Yu
Aug 21, 2019·Journal of Clinical Medicine·Kyu Yeong ChoiAlzheimer's Disease Neuroimaging Initative
Nov 9, 2018·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Rong ChengChristiane Reitz
Feb 19, 2017·Neurology·Giuseppe TostoRichard Mayeux
Aug 22, 2017·Current Neurology and Neuroscience Reports·Neha Raghavan, Giuseppe Tosto
Aug 2, 2019·International Journal of Molecular Sciences·Pratip RanaPreetam Ghosh
Sep 14, 2016·Molecular and Cellular Probes·Giuseppe Tosto, Christiane Reitz
Apr 6, 2021·Frontiers in Aging Neuroscience·David VogrincVita Dolžan
Apr 24, 2021·Brain : a Journal of Neurology·Nadia DehghaniRita Guerreiro

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Methods Mentioned

BETA
genotyping
chip
transgenic
ubiquitination

Software Mentioned

R
ImageJ
Haploview
IMPUTE2
IGAP
varLD
GWAF
ADMIXTURE
CaTS
PLINK

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