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A Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies.

TitleA Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies.
Publication TypeJournal Article
Year of Publication2023
AuthorsSrinivasan, S, Wu, P, Mercader, JM, Udler, MS, Porneala, BC, Bartz, TM, Floyd, JS, Sitlani, C, Guo, X, Haessler, J, Kooperberg, C, Liu, J, Ahmad, S, van Duijn, C, Liu, C-T, Goodarzi, MO, Florez, JC, Meigs, JB, Rotter, JI, Rich, SS, Dupuis, J, Leong, A
JournalJ Endocr Soc
Volume7
Issue11
Paginationbvad123
Date Published2023 Oct 09
ISSN2472-1972
Abstract<p><b>CONTEXT: </b>Both type 1 diabetes (T1D) and type 2 diabetes (T2D) have significant genetic contributions to risk and understanding their overlap can offer clinical insight.</p><p><b>OBJECTIVE: </b>We examined whether a T1D polygenic score (PS) was associated with a diagnosis of T2D in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.</p><p><b>METHODS: </b>We constructed a T1D PS using 79 known single nucleotide polymorphisms associated with T1D risk. We analyzed 13 792 T2D cases and 14 169 controls from CHARGE cohorts to determine the association between the T1D PS and T2D prevalence. We validated findings in an independent sample of 2256 T2D cases and 27 052 controls from the Mass General Brigham Biobank (MGB Biobank). As secondary analyses in 5228 T2D cases from CHARGE, we used multivariable regression models to assess the association of the T1D PS with clinical outcomes associated with T1D.</p><p><b>RESULTS: </b>The T1D PS was not associated with T2D both in CHARGE ( = .15) and in the MGB Biobank ( = .87). The partitioned human leukocyte antigens only PS was associated with T2D in CHARGE (OR 1.02 per 1 SD increase in PS, 95% CI 1.01-1.03, = .006) but not in the MGB Biobank. The T1D PS was weakly associated with insulin use (OR 1.007, 95% CI 1.001-1.012, = .03) in CHARGE T2D cases but not with other outcomes.</p><p><b>CONCLUSION: </b>In large biobank samples, a common variant PS for T1D was not consistently associated with prevalent T2D. However, possible heterogeneity in T2D cannot be ruled out and future studies are needed do subphenotyping.</p>
DOI10.1210/jendso/bvad123
Alternate JournalJ Endocr Soc
PubMed ID37841955
PubMed Central IDPMC10576255
Grant List75N92020D00005 / HL / NHLBI NIH HHS / United States
75N92021D00005 / WH / WHI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
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HHSN268201500003I / HL / NHLBI NIH HHS / United States
75N92021D00004 / WH / WHI NIH HHS / United States
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75N92021D00002 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
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R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
K23 DK120932 / DK / NIDDK NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
75N92020D00001 / HL / NHLBI NIH HHS / United States
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R01 HL105756 / HL / NHLBI NIH HHS / United States
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75N92021D00001 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
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HHSN268201500001I / HL / NHLBI NIH HHS / United States
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UL1 TR001420 / TR / NCATS NIH HHS / United States
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75N92019D00031 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
R01 HL151855 / HL / NHLBI NIH HHS / United States
UM1 DK078616 / DK / NIDDK NIH HHS / United States
75N92020D00006 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
K24 HL157960 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
ePub date: 
23/10