First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

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Cousminer, Diana LThe Children's Hospital of Philadelphia,University of Pennsylvania (author)

First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

Article/chapterEnglish2018

Publisher, publication year, extent ...

2018-10-15
American Diabetes Association,2018

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LIBRIS-ID:oai:lup.lub.lu.se:2c0a68de-7a5f-4688-99e7-e81d87bb4894
https://lup.lub.lu.se/record/2c0a68de-7a5f-4688-99e7-e81d87bb4894URI
https://doi.org/10.2337/dc18-1032DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTS: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONS: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reumatologi och inflammation hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Rheumatology and Autoimmunity hsv//eng
Adult
Aged
Case-Control Studies
Diabetes Mellitus, Type 1/genetics
Diabetes Mellitus, Type 2/genetics
Female
Genome-Wide Association Study
Glucose Intolerance/genetics
Haplotypes
Humans
Immune System Phenomena/genetics
Insulin/metabolism
Latent Autoimmune Diabetes in Adults/genetics
Male
Middle Aged
Young Adult
ANDIS
diabetes
diabetics

Added entries (persons, corporate bodies, meetings, titles ...)

Ahlqvist, EmmaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)infl-eah (author)
Åkerlund, MikaelLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medk-mak (author)
Melander, OlleLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome (author)
Voight, Benjamin FUniversity of Pennsylvania(Swepub:lu)med-bf_ (author)
Tuomi, TiinamaijaInstitute for Molecular Medicine Finland (FIMM),Helsinki University Central Hospital,University of Helsinki(Swepub:lu)ti8736tu (author)
Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Institute for Molecular Medicine Finland (FIMM),Skåne University Hospital(Swepub:lu)endo-lgr (author)
Leslie, R. DavidQueen Mary University (author)
Grant, Struan F AThe Children's Hospital of Philadelphia,University of Pennsylvania (author)
The Children's Hospital of PhiladelphiaUniversity of Pennsylvania (creator_code:org_t)
Bone Mineral Density in Childhood Study

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In:Diabetes Care: American Diabetes Association41:11, s. 2396-24031935-55480149-5992

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