Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1.
Dizziness
Genome-wide association studies
Human
Imbalance
Vertigo
Journal
Journal of the Association for Research in Otolaryngology : JARO
ISSN: 1438-7573
Titre abrégé: J Assoc Res Otolaryngol
Pays: United States
ID NLM: 100892857
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
06
02
2023
accepted:
12
11
2023
medline:
1
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
aheadofprint
Résumé
Chronic age-related imbalance is a common cause of falls and subsequent death in the elderly and can arise from dysfunction of the vestibular system, an elegant neuroanatomical group of pathways that mediates human perception of acceleration, gravity, and angular head motion. Studies indicate that 27-46% of the risk of age-related chronic imbalance is genetic; nevertheless, the underlying genes remain unknown. The cohort consisted of 50,339 cases and 366,900 controls in the Million Veteran Program. The phenotype comprised cases with two ICD diagnoses of vertigo or dizziness at least 6 months apart, excluding acute or recurrent vertiginous syndromes and other non-vestibular disorders. Genome-wide association studies were performed as individual logistic regressions on European, African American, and Hispanic ancestries followed by trans-ancestry meta-analysis. Downstream analysis included case-case-GWAS, fine mapping, probabilistic colocalization of significant variants and genes with eQTLs, and functional analysis of significant hits. Two significant loci were identified in Europeans, another in the Hispanic population, and two additional in trans-ancestry meta-analysis, including three novel loci. Fine mapping revealed credible sets of intronic single nucleotide polymorphisms (SNPs) in MLLT10 - a histone methyl transferase cofactor, BPTF - a subunit of a nucleosome remodeling complex implicated in neurodevelopment, and LINC01224 - a proto-oncogene receptor tyrosine kinase. Despite the difficulties of phenotyping the nature of chronic imbalance, we replicated two loci from previous vertigo GWAS studies and identified three novel loci. Findings suggest candidates for further study and ultimate treatment of this common elderly disorder.
Identifiants
pubmed: 38036714
doi: 10.1007/s10162-023-00917-y
pii: 10.1007/s10162-023-00917-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R01DC020052
Pays : United States
Organisme : NIH HHS
ID : R01GM140287
Pays : United States
Investigateurs
Sumitra Muralidhar
(S)
Jennifer Moser
(J)
Jennifer E Deen
(JE)
Philip S Tsao
(PS)
J Michael Gaziano
(JM)
Elizabeth Hauser
(E)
Amy Kilbourne
(A)
Shiuh-Wen Luoh
(SW)
Michael Matheny
(M)
Dave Oslin
(D)
Lori Churby
(L)
Stacey B Whitbourne
(SB)
Jessica V Brewer
(JV)
Shahpoor Alex Shayan
(SA)
Luis E Selva
(LE)
Saiju Pyarajan
(S)
Kelly Cho
(K)
Scott L DuVall
(SL)
Mary T Brophy
(MT)
Brady Stephens
(B)
Todd Connor
(T)
Dean P Argyres
(DP)
Tim Assimes
(T)
Adriana Hung
(A)
Henry Kranzler
(H)
Samuel Aguayo
(S)
Sunil Ahuja
(S)
Kathrina Alexander
(K)
Xiao M Androulakis
(XM)
Prakash Balasubramanian
(P)
Zuhair Ballas
(Z)
Jean Beckham
(J)
Sujata Bhushan
(S)
Edward Boyko
(E)
David Cohen
(D)
Louis Dellitalia
(L)
L Christine Faulk
(LC)
Joseph Fayad
(J)
Daryl Fujii
(D)
Saib Gappy
(S)
Frank Gesek
(F)
Jennifer Greco
(J)
Michael Godschalk
(M)
Todd W Gress
(TW)
Samir Gupta
(S)
Salvador Gutierrez
(S)
John Harley
(J)
Kimberly Hammer
(K)
Mark Hamner
(M)
Adriana Hung
(A)
Robin Hurley
(R)
Pran Iruvanti
(P)
Frank Jacono
(F)
Darshana Jhala
(D)
Scott Kinlay
(S)
Jon Klein
(J)
Michael Landry
(M)
Peter Liang
(P)
Suthat Liangpunsakul
(S)
Jack Lichy
(J)
C Scott Mahan
(CS)
Ronnie Marrache
(R)
Stephen Mastorides
(S)
Elisabeth Mates
(E)
Kristin Mattocks
(K)
Paul Meyer
(P)
Jonathan Moorman
(J)
Timothy Morgan
(T)
Maureen Murdoch
(M)
James Norton
(J)
Olaoluwa Okusaga
(O)
Kris Ann Oursler
(KA)
Ana Palacio
(A)
Samuel Poon
(S)
Emily Potter
(E)
Michael Rauchman
(M)
Richard Servatius
(R)
Satish Sharma
(S)
River Smith
(R)
Peruvemba Sriram
(P)
Patrick Strollo
(P)
Neeraj Tandon
(N)
Gerardo Villareal
(G)
Agnes Wallbom
(A)
Jessica Walsh
(J)
John Wells
(J)
Jeffrey Whittle
(J)
Mary Whooley
(M)
Allison E Williams
(AE)
Peter Wilson
(P)
Junzhe Xu
(J)
Shing Shing Yeh
(SS)
Daniel Dochtermann
(D)
Poornima Devineni
(P)
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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