Search: WFRF:(Harden A)
> (2020-2023) >
Identification of G...
-
Li, Josephine H.Massachusetts General Hospital,Broad Institute,Harvard Medical School
(author)
Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
- Article/chapterEnglish2023
Publisher, publication year, extent ...
-
2022-12-16
-
American Diabetes Association,2023
-
12 s.
Numbers
-
LIBRIS-ID:oai:lup.lub.lu.se:9c6b3577-af2a-4937-9e0d-3125bd080e0e
-
https://lup.lub.lu.se/record/9c6b3577-af2a-4937-9e0d-3125bd080e0eURI
-
https://doi.org/10.2337/db22-0702DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:art swepub-publicationtype
-
Subject category:ref swepub-contenttype
Notes
-
Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Perry, James A.University of Maryland School of Medicine
(author)
-
Jablonski, Kathleen A.George Washington University
(author)
-
Srinivasan, ShylajaUniversity of California, San Francisco
(author)
-
Chen, LingMassachusetts General Hospital,Broad Institute
(author)
-
Todd, Jennifer N.Boston Children's Hospital,Broad Institute,Massachusetts General Hospital
(author)
-
Harden, MaeganBroad Institute
(author)
-
Mercader, Josep M.Broad Institute,Massachusetts General Hospital,Harvard Medical School
(author)
-
Pan, QingGeorge Washington University
(author)
-
Dawed, Adem Y.University of Dundee
(author)
-
Yee, Sook WahUniversity of California, San Francisco
(author)
-
Pearson, Ewan R.University of Dundee
(author)
-
Giacomini, Kathleen M.University of California, San Francisco
(author)
-
Giri, AyushVanderbilt University Medical Center
(author)
-
Hung, Adriana M.Vanderbilt University Medical Center
(author)
-
Xiao, ShujieHenry Ford Health System
(author)
-
Williams, L. KeokiHenry Ford Health System
(author)
-
Franks, Paul W.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf
(author)
-
Hanson, Robert L.National Institute of Diabetes and Digestive and Kidney Diseases
(author)
-
Kahn, Steven E.Washington University School of Medicine
(author)
-
Knowler, William C.National Institute of Diabetes and Digestive and Kidney Diseases
(author)
-
Pollin, Toni I.University of Maryland School of Medicine
(author)
-
Florez, Jose C.Harvard Medical School,Broad Institute,Massachusetts General Hospital
(author)
-
Massachusetts General HospitalBroad Institute
(creator_code:org_t)
Related titles
-
In:Diabetes: American Diabetes Association72:8, s. 1161-11720012-17971939-327X
Internet link
Find in a library
-
Diabetes
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
Li, Josephine H.
-
Perry, James A.
-
Jablonski, Kathl ...
-
Srinivasan, Shyl ...
-
Chen, Ling
-
Todd, Jennifer N ...
-
show more...
-
Harden, Maegan
-
Mercader, Josep ...
-
Pan, Qing
-
Dawed, Adem Y.
-
Yee, Sook Wah
-
Pearson, Ewan R.
-
Giacomini, Kathl ...
-
Giri, Ayush
-
Hung, Adriana M.
-
Xiao, Shujie
-
Williams, L. Keo ...
-
Franks, Paul W.
-
Hanson, Robert L ...
-
Kahn, Steven E.
-
Knowler, William ...
-
Pollin, Toni I.
-
Florez, Jose C.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Endocrinology an ...
- Articles in the publication
-
Diabetes
- By the university
-
Lund University