Search: WFRF:(Lindgren Anders E. G.) >
Loci for insulin pr...
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
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Broadaway, K Alaine (author)
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Yin, Xianyong (author)
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Williamson, Alice (author)
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show more...
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Parsons, Victoria A (author)
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Wilson, Emma P (author)
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Moxley, Anne H (author)
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Vadlamudi, Swarooparani (author)
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Varshney, Arushi (author)
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Jackson, Anne U (author)
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Ahuja, Vasudha (author)
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Bornstein, Stefan R (author)
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Corbin, Laura J (author)
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Delgado, Graciela E (author)
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Dwivedi, Om P (author)
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Silva, Lilian Fernandes (author)
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Frayling, Timothy M (author)
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Grallert, Harald (author)
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- Gustafsson, Stefan (author)
- Uppsala universitet,Klinisk epidemiologi
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Hakaste, Liisa (author)
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- Hammar, Ulf (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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Herder, Christian (author)
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Herrmann, Sandra (author)
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Højlund, Kurt (author)
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Hughes, David A (author)
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Kleber, Marcus E (author)
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Lindgren, Cecilia M (author)
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Liu, Ching-Ti (author)
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Luan, Jian'an (author)
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Malmberg, Anni (author)
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Moissl, Angela P (author)
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Morris, Andrew P (author)
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Perakakis, Nikolaos (author)
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Peters, Annette (author)
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Petrie, John R (author)
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Roden, Michael (author)
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Schwarz, Peter E H (author)
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Sharma, Sapna (author)
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- Silveira, Angela (author)
- Karolinska Institutet
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- Strawbridge, Rona J (author)
- Karolinska Institutet
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Tuomi, Tiinamaija (author)
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Wood, Andrew R (author)
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Wu, Peitao (author)
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- Zethelius, Björn (author)
- Uppsala universitet,Geriatrik
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Baldassarre, Damiano (author)
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Eriksson, Johan G (author)
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- Fall, Tove, 1979- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi
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Florez, Jose C (author)
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Fritsche, Andreas (author)
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- Gigante, Bruna (author)
- Karolinska Institutet
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Hamsten, Anders (author)
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Kajantie, Eero (author)
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Laakso, Markku (author)
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Lahti, Jari (author)
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Lawlor, Deborah A (author)
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- Lind, Lars (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Centrum för klinisk forskning, Gävleborg,Uppsala kliniska forskningscentrum (UCR),Kardiologi,Geriatrik,Klinisk nutrition och metabolism,Molekylär epidemiologi,Radiologi,Klinisk epidemiologi
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März, Winfried (author)
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Meigs, James B (author)
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- Sundström, Johan, Professor, 1971- (author)
- Uppsala universitet,Geriatrik,Uppsala kliniska forskningscentrum (UCR),Kardiologi,Science for Life Laboratory, SciLifeLab,Klinisk epidemiologi,Arbets- och miljömedicin
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Timpson, Nicholas J (author)
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Wagner, Robert (author)
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Walker, Mark (author)
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Wareham, Nicholas J (author)
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Watkins, Hugh (author)
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Barroso, Inês (author)
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O'Rahilly, Stephen (author)
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Grarup, Niels (author)
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Parker, Stephen Cj (author)
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Boehnke, Michael (author)
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Langenberg, Claudia (author)
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Wheeler, Eleanor (author)
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Mohlke, Karen L (author)
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- English.
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In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
Close
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- GWAS
- colocalization
- conditional
- eQTL
- enhancer
- fine-mapping
- meta-analysis
- proinsulin
- signal
- type 2 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Broadaway, K Ala ...
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Yin, Xianyong
-
Williamson, Alic ...
-
Parsons, Victori ...
-
Wilson, Emma P
-
Moxley, Anne H
-
show more...
-
Vadlamudi, Swaro ...
-
Varshney, Arushi
-
Jackson, Anne U
-
Ahuja, Vasudha
-
Bornstein, Stefa ...
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Corbin, Laura J
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Delgado, Graciel ...
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Dwivedi, Om P
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Silva, Lilian Fe ...
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Frayling, Timoth ...
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Grallert, Harald
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Gustafsson, Stef ...
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Hakaste, Liisa
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Hammar, Ulf
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Herder, Christia ...
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Herrmann, Sandra
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Højlund, Kurt
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Hughes, David A
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Kleber, Marcus E
-
Lindgren, Cecili ...
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Liu, Ching-Ti
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Luan, Jian'an
-
Malmberg, Anni
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Moissl, Angela P
-
Morris, Andrew P
-
Perakakis, Nikol ...
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Peters, Annette
-
Petrie, John R
-
Roden, Michael
-
Schwarz, Peter E ...
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Sharma, Sapna
-
Silveira, Angela
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Strawbridge, Ron ...
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Tuomi, Tiinamaij ...
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Wood, Andrew R
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Wu, Peitao
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Zethelius, Björn
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Baldassarre, Dam ...
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Eriksson, Johan ...
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Fall, Tove, 1979 ...
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Florez, Jose C
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Fritsche, Andrea ...
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Gigante, Bruna
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Hamsten, Anders
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Kajantie, Eero
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Laakso, Markku
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Lahti, Jari
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Lawlor, Deborah ...
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Lind, Lars
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März, Winfried
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Meigs, James B
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Sundström, Johan ...
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Timpson, Nichola ...
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Wagner, Robert
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Walker, Mark
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Wareham, Nichola ...
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Watkins, Hugh
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Barroso, Inês
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O'Rahilly, Steph ...
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Grarup, Niels
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Parker, Stephen ...
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Boehnke, Michael
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Langenberg, Clau ...
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Wheeler, Eleanor
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Mohlke, Karen L
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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American Journal ...
- By the university
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Uppsala University
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Karolinska Institutet