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Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets.
Ramos, Jairo; Caywood, Laura J; Prough, Michael B; Clouse, Jason E; Herington, Sharlene D; Slifer, Susan H; Fuzzell, M Denise; Fuzzell, Sarada L; Hochstetler, Sherri D; Miskimen, Kristy L; Main, Leighanne R; Osterman, Michael D; Zaman, Andrew F; Whitehead, Patrice L; Adams, Larry D; Laux, Renee A; Song, Yeunjoo E; Foroud, Tatiana M; Mayeux, Richard P; St George-Hyslop, Peter; Ogrocki, Paula K; Lerner, Alan J; Vance, Jeffery M; Cuccaro, Michael L; Haines, Jonathan L; Pericak-Vance, Margaret A; Scott, William K.
Afiliação
  • Ramos J; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Caywood LJ; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Prough MB; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Clouse JE; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Herington SD; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Slifer SH; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Fuzzell MD; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Fuzzell SL; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Hochstetler SD; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Miskimen KL; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Main LR; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Osterman MD; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Zaman AF; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Whitehead PL; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Adams LD; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Laux RA; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Song YE; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Foroud TM; Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Mayeux RP; Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • St George-Hyslop P; Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, USA.
  • Ogrocki PK; Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
  • Lerner AJ; Department of Neurology, Columbia University, New York, New York, USA.
  • Vance JM; University of Toronto, Toronto, Ontario, Canada.
  • Cuccaro ML; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
  • Haines JL; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
  • Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School, of Medicine, Miami, Florida, USA.
  • Scott WK; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Alzheimers Dement ; 19(2): 611-620, 2023 02.
Article em En | MEDLINE | ID: mdl-35490390
ABSTRACT

INTRODUCTION:

Studies of cognitive impairment (CI) in Amish communities have identified sibships containing CI and cognitively unimpaired (CU) individuals. We hypothesize that CU individuals may carry protective alleles delaying age at onset (AAO) of CI.

METHODS:

A total of 1522 individuals screened for CI were genotyped. The outcome studied was AAO for CI individuals or age at last normal exam for CU individuals. Cox mixed-effects models examined association between age and single nucleotide variants (SNVs).

RESULTS:

Three SNVs were significantly associated (P < 5 × 10-8 ) with AAO on chromosomes 6 (rs14538074; hazard ratio [HR] = 3.35), 9 (rs534551495; HR = 2.82), and 17 (rs146729640; HR = 6.38). The chromosome 17 association was replicated in the independent National Institute on Aging Genetics Initiative for Late-Onset Alzheimer's Disease dataset.

DISCUSSION:

The replicated genome-wide significant association with AAO on chromosome 17 is located in the SHISA6 gene, which is involved in post-synaptic transmission in the hippocampus and is a biologically plausible candidate gene for Alzheimer's disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos