Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.

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Fältnamn	Indikatorer	Metadata
000		06187naa a2201141 4500
001		oai:gup.ub.gu.se/196064
003		SwePub
008		240528s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:129091865
009		oai:DiVA.org:uu-228006
024	7	a https://gup.ub.gu.se/publication/1960642 URI
024	7	a https://doi.org/10.2337/db13-09492 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1290918652 URI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2280062 URI
040		a (SwePub)gud (SwePub)kid (SwePub)uu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Dimas, Antigone S4 aut
245	1 0	a Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.
264		c 2014-05-15
264	1	b American Diabetes Association,c 2014
500		a De fem sista författarna delar sistaförfattarskapet.
520		a Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci and indices of proinsulin processing, insulin secretion and insulin sensitivity. We included data from up to 58,614 non-diabetic subjects with basal measures, and 17,327 with dynamic measures. We employed additive genetic models with adjustment for sex, age and BMI, followed by fixed-effects inverse variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (including TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without detectable change in fasting glucose. The final group contained twenty risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
700	1	a Lagou, Vasiliki4 aut
700	1	a Barker, Adam4 aut
700	1	a Knowles, Joshua W4 aut
700	1	a Mägi, Reedik4 aut
700	1	a Hivert, Marie-France4 aut
700	1	a Benazzo, Andrea4 aut
700	1	a Rybin, Denis4 aut
700	1	a Jackson, Anne U4 aut
700	1	a Stringham, Heather M4 aut
700	1	a Song, Ciu Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi4 aut0 (Swepub:uu)ciaso492
700	1	a Fischer-Rosinsky, Antje4 aut
700	1	a Boesgaard, Trine Welløv4 aut
700	1	a Grarup, Niels4 aut
700	1	a Abbasi, Fahim A4 aut
700	1	a Lind, Larsu Uppsala universitet,Kardiovaskulär epidemiologi4 aut0 (Swepub:uu)larslind
700	1	a Hao, Ke4 aut
700	1	a Yang, Xia4 aut
700	1	a Lecoeur, Cécile4 aut
700	1	a Barroso, Inês4 aut
700	1	a Bonnycastle, Lori L4 aut
700	1	a Böttcher, Yvonne4 aut
700	1	a Bumpstead, Suzannah4 aut
700	1	a Chines, Peter S4 aut
700	1	a Erdos, Michael R4 aut
700	1	a Graessler, Jurgen4 aut
700	1	a Kovacs, Peter4 aut
700	1	a Morken, Mario A4 aut
700	1	a Narisu, Narisu4 aut
700	1	a Payne, Felicity4 aut
700	1	a Stancakova, Alena4 aut
700	1	a Swift, Amy J4 aut
700	1	a Tönjes, Anke4 aut
700	1	a Bornstein, Stefan R4 aut
700	1	a Cauchi, Stéphane4 aut
700	1	a Froguel, Philippe4 aut
700	1	a Meyre, David4 aut
700	1	a Schwarz, Peter E H4 aut
700	1	a Häring, Hans-Ulrich4 aut
700	1	a Smith, Ulf,d 1943u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xsmiul
700	1	a Boehnke, Michael4 aut
700	1	a Bergman, Richard N4 aut
700	1	a Collins, Francis S4 aut
700	1	a Mohlke, Karen L4 aut
700	1	a Tuomilehto, Jaakko4 aut
700	1	a Quertemous, Thomas4 aut
700	1	a Lind, Lars4 aut
700	1	a Hansen, Torben4 aut
700	1	a Pedersen, Oluf4 aut
700	1	a Walker, Mark4 aut
700	1	a Pfeiffer, Andreas F H4 aut
700	1	a Spranger, Joachim4 aut
700	1	a Stumvoll, Michael4 aut
700	1	a Meigs, James B4 aut
700	1	a Wareham, Nicholas J4 aut
700	1	a Kuusisto, Johanna4 aut
700	1	a Laakso, Markku4 aut
700	1	a Langenberg, Claudia4 aut
700	1	a Dupuis, Josée4 aut
700	1	a Watanabe, Richard M4 aut
700	1	a Florez, Jose C4 aut
700	1	a Ingelsson, Eriku Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ering425
700	1	a McCarthy, Mark I4 aut
700	1	a Prokopenko, Inga4 aut
700	1	a MAGIC Investigators,4 aut
710	2	a Uppsala universitetb Science for Life Laboratory, SciLifeLab4 org
773	0	t Diabetesd : American Diabetes Associationg 63:6, s. 2158-2171q 63:6<2158-2171x 1939-327Xx 0012-1797
856	4	u https://diabetes.diabetesjournals.org/content/diabetes/63/6/2158.full.pdf
856	4 8	u https://gup.ub.gu.se/publication/196064
856	4 8	u https://doi.org/10.2337/db13-0949
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:129091865
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-228006

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Av författaren/redakt...: Dimas, Antigone ...; Lagou, Vasiliki; Barker, Adam; Knowles, Joshua ...; Mägi, Reedik; Hivert, Marie-Fr ...; visa fler...; Benazzo, Andrea; Rybin, Denis; Jackson, Anne U; Stringham, Heath ...; Song, Ci; Fischer-Rosinsky ...; Boesgaard, Trine ...; Grarup, Niels; Abbasi, Fahim A; Lind, Lars; Hao, Ke; Yang, Xia; Lecoeur, Cécile; Barroso, Inês; Bonnycastle, Lor ...; Böttcher, Yvonne; Bumpstead, Suzan ...; Chines, Peter S; Erdos, Michael R; Graessler, Jurge ...; Kovacs, Peter; Morken, Mario A; Narisu, Narisu; Payne, Felicity; Stancakova, Alen ...; Swift, Amy J; Tönjes, Anke; Bornstein, Stefa ...; Cauchi, Stéphane; Froguel, Philipp ...; Meyre, David; Schwarz, Peter E ...; Häring, Hans-Ulr ...; Smith, Ulf, 1943; Boehnke, Michael; Bergman, Richard ...; Collins, Francis ...; Mohlke, Karen L; Tuomilehto, Jaak ...; Quertemous, Thom ...; Hansen, Torben; Pedersen, Oluf; Walker, Mark; Pfeiffer, Andrea ...; Spranger, Joachi ...; Stumvoll, Michae ...; Meigs, James B; Wareham, Nichola ...; Kuusisto, Johann ...; Laakso, Markku; Langenberg, Clau ...; Dupuis, Josée; Watanabe, Richar ...; Florez, Jose C; Ingelsson, Erik; McCarthy, Mark I; Prokopenko, Inga; MAGIC Investigat ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

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