Genetic Insights Into Frailty: Association of 9p21-23 Locus With Frailty

Frontiers in Medicine
Sanish SathyanJoe Verghese

Abstract

Frailty is a complex aging phenotype associated with increased vulnerability to disability and death. Understanding the biological antecedents of frailty may provide clues to healthy aging. The genome-wide association study hotspot, 9p21-23 region, is a risk locus for a number of age-related complex disorders associated with frailty. Hence, we conducted an association study to examine whether variations in 9p21-23 locus plays a role in the pathogenesis of frailty in 637 community-dwelling Ashkenazi Jewish adults aged 65 and older enrolled in the LonGenity study. The strongest association with frailty (adjusted for age and gender) was found with the SNP rs518054 (odds ratio: 1.635, 95% CI = 1.241-2.154; p-value: 4.81 × 10-04) intergenic and located between LOC105375977 and C9orf146. The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer...Continue Reading

References

Jan 1, 1982·Journal of Psychiatric Research·J A YesavageV O Leirer
Mar 17, 2001·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·L P FriedUNKNOWN Cardiovascular Health Study Collaborative Research Group
Mar 17, 2001·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·A B NewmanUNKNOWN Cardiovascular Health Study Research Group
Dec 26, 2001·Archives of Internal Medicine·T R FriedM E Tinetti
May 2, 2002·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Walter M Bortz
May 25, 2002·Science·Stacey B GabrielDavid Altshuler
Sep 27, 2003·Journal of the American Geriatrics Society·Richard B LiptonHerman Buschke
Oct 16, 2003·JAMA : the Journal of the American Medical Association·Nir BarzilaiAlan R Shuldiner
Jan 30, 2004·Science of Aging Knowledge Environment : SAGE KE·Jeremy Walston
Mar 20, 2004·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Linda P FriedGerard Anderson
Jun 25, 2004·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Arnold B MitnitskiKenneth Rockwood
Jul 13, 2004·Mechanisms of Ageing and Development·Kenneth RockwoodArnold Mitnitski
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Jan 6, 2005·Molecular and Cellular Biology·George Steele-PerkinsRichard M Gronostajski
Feb 18, 2005·Nature Reviews. Genetics·Joel N Hirschhorn, Mark J Daly
Aug 5, 2005·Journal of the American Geriatrics Society·Nancy Fugate WoodsUNKNOWN Women's Health Initiative
May 25, 2006·Bioinformatics·Xavier SoléVíctor Moreno
Oct 18, 2006·Journal of Advanced Nursing·Merry-Jo LeversJanet C Ross Kerr
Jan 24, 2007·Journal of Neurology, Neurosurgery, and Psychiatry·Joe VergheseXiaonan Xue
Feb 3, 2007·Postgraduate Medical Journal·Frank Lally, Peter Crome
Mar 21, 2007·PLoS Genetics·Paul D P PharoahUNKNOWN SEARCH Investigators
Apr 13, 2007·Breast Cancer Research : BCR·Caroline BaynesUNKNOWN SEARCH breast cancer study
Apr 27, 2007·Mechanisms of Ageing and Development·David MelzerPaul D Pharoah
May 5, 2007·Science·Anna HelgadottirKari Stefansson
Jun 9, 2007·Psychosomatic Medicine·Aron S BuchmanDavid A Bennett
Jul 20, 2007·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Kenneth Rockwood, Arnold Mitnitski
Jul 20, 2007·The New England Journal of Medicine·Nilesh J SamaniUNKNOWN WTCCC and the Cardiogenics Consortium
Nov 8, 2007·Nucleic Acids Research·Phil Hyoun Lee, Hagit Shatkay
Jul 29, 2008·Nature Genetics·Barbara SchormairJuliane Winkelmann
Aug 13, 2008·Neurology·Aron S BuchmanDavid A Bennett
Nov 11, 2008·Nature Genetics·Kaya BilguvarMurat Günel
Nov 21, 2008·Journal of Internal Medicine·H M BjörckP Eriksson
Dec 9, 2008·Archives of Physical Medicine and Rehabilitation·Jennifer S BrachAnne B Newman
May 26, 2009·The American Journal of Cardiology·Jonathan AfilaloHoward Bergman
May 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Selvaraju VeeriahTimothy A Chan
Jul 7, 2009·Nature Genetics·D Timothy BishopJulia A Newton Bishop
Jul 15, 2009·Nature Genetics·Emelia J BenjaminJacqueline C M Witteman
Aug 12, 2009·Neurobiology of Aging·Enzo EmanuelePierluigi Politi
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Gil AtzmonYousin Suh
Dec 25, 2009·Circulation. Cardiovascular Genetics·Christie CluettDavid Melzer
Jun 19, 2010·Biogerontology·T FulopG Pawelec
Aug 31, 2010·Lancet Neurology·Hannu LaaksovirtaBryan J Traynor
Oct 20, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric PasmantIvan Bièche

❮ Previous
Next ❯

Citations

Jul 31, 2020·Biodemography and Social Biology·Breanne L Newell-StamperBenjamin W Domingue
Aug 28, 2019·Journal of Alzheimer's Disease : JAD·Sanish SathyanJoe Verghese
Apr 17, 2020·Disease Models & Mechanisms·Alon DayaDavid Karasik
Aug 8, 2020·Aging Cell·Sanish SathyanJoe Verghese
Mar 7, 2021·International Journal of Environmental Research and Public Health·José Luis García-GiménezFederico V Pallardó

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping

Software Mentioned

FuncPred
GAITRite
Regulome
GTEx
Genotype
Tissue Expression portal ( GTEx )
SNPStats
Plink
SPSS
Haploview

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Genetics & Epigenetics of Aging

Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.