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First Genome-Wide A...
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 L (author)
- The Children's Hospital of Philadelphia,University of Pennsylvania
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- Ahlqvist, Emma (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Åkerlund, Mikael (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Skåne University Hospital
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- Melander, Olle (author)
- Lund 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
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- Voight, Benjamin F (author)
- University of Pennsylvania
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- Tuomi, Tiinamaija (author)
- Institute for Molecular Medicine Finland (FIMM),University of Helsinki,Helsinki University Central Hospital
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- Groop, Leif (author)
- Lund 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
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- Leslie, R. David (author)
- Queen Mary University
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- Grant, Struan F A (author)
- University of Pennsylvania,The Children's Hospital of Philadelphia
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(creator_code:org_t)
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- 2018-10-15
- 2018
- English.
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:11, s. 2396-2403
- Related links:
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http://dx.doi.org/10...
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https://care.diabete...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- 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
- 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)
Keyword
- 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
Publication and Content Type
- art (subject category)
- ref (subject category)
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