Heterogeneous associations between interleukin-6 receptor variants and phenotypes across ancestries and implications for therapy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 Apr 2024
05 Apr 2024
Historique:
received:
13
01
2023
accepted:
08
02
2024
medline:
6
4
2024
pubmed:
6
4
2024
entrez:
5
4
2024
Statut:
epublish
Résumé
The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10
Identifiants
pubmed: 38580710
doi: 10.1038/s41598-024-54063-3
pii: 10.1038/s41598-024-54063-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8021Investigateurs
Sumitra Muralidhar
(S)
Jennifer Moser
(J)
Jennifer E Deen
(JE)
Philip S Tsao
(PS)
Sumitra Muralidhar
(S)
J Michael Gaziano
(JM)
Elizabeth Hauser
(E)
Amy Kilbourne
(A)
Shiuh-Wen Luoh
(SW)
Michael Matheny
(M)
Dave Oslin
(D)
J Michael Gaziano
(JM)
Philip S Tsao
(PS)
Lori Churby
(L)
Stacey B Whitbourne
(SB)
Jessica V Brewer
(JV)
Shahpoor Shayan
(S)
Luis E Selva
(LE)
Saiju Pyarajan
(S)
Kelly Cho
(K)
Scott L DuVall
(SL)
Mary T Brophy
(MT)
J Michael Gaziano
(JM)
Philip S Tsao
(PS)
Brady Stephens
(B)
Todd Connor
(T)
Themistocles L Assimes
(TL)
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)
Philip Tsao
(P)
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)
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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