Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases

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Fältnamn	Indikatorer	Metadata
000		06843naa a2201213 4500
001		oai:lup.lub.lu.se:065336c1-4e0b-4762-9502-a33a047533a0
003		SwePub
008		160401s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/28956612 URI
024	7	a https://doi.org/10.1371/journal.pgen.10027412 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Perry, John R. B.4 aut
245	1 0	a Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases
264		c 2012-05-31
264	1	b Public Library of Science (PLoS),c 2012
338		a electronic2 rdacarrier
520		a Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m(2)) compared to obese cases (BMI >= 30 Kg/m(2)). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m(2)) or 4,123 obese cases (BMI >= 30 kg/m(2)), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4610 29, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A-previously identified in South Asians but not Europeans-was associated with type 2 diabetes in obese cases (P = 1.3 x 10(-8), OR= 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2 x 10(-14). This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2 x 10(-16). This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.
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 Voight, Benjamin F.4 aut
700	1	a Yengo, Loic4 aut
700	1	a Amin, Najaf4 aut
700	1	a Dupuis, Josee4 aut
700	1	a Ganser, Martha4 aut
700	1	a Grallert, Harald4 aut
700	1	a Navarro, Pau4 aut
700	1	a Li, Man4 aut
700	1	a Qi, Lu4 aut
700	1	a Steinthorsdottir, Valgerdur4 aut
700	1	a Scott, Robert A.4 aut
700	1	a Almgren, Peteru Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups4 aut0 (Swepub:lu)endo-pal
700	1	a Arking, Dan E.4 aut
700	1	a Aulchenko, Yurii4 aut
700	1	a Balkau, Beverley4 aut
700	1	a Benediktsson, Rafn4 aut
700	1	a Bergman, Richard N.4 aut
700	1	a Boerwinkle, Eric4 aut
700	1	a Bonnycastle, Lori4 aut
700	1	a Burtt, Noel P.4 aut
700	1	a Campbell, Harry4 aut
700	1	a Charpentier, Guillaume4 aut
700	1	a Collins, Francis S.4 aut
700	1	a Gieger, Christian4 aut
700	1	a Green, Todd4 aut
700	1	a Hadjadj, Samy4 aut
700	1	a Hattersley, Andrew T.4 aut
700	1	a Herder, Christian4 aut
700	1	a Hofman, Albert4 aut
700	1	a Johnson, Andrew D.4 aut
700	1	a Kottgen, Anna4 aut
700	1	a Kraft, Peter4 aut
700	1	a Labrune, Yann4 aut
700	1	a Langenberg, Claudia4 aut
700	1	a Manning, Alisa K.4 aut
700	1	a Mohlke, Karen L.4 aut
700	1	a Morris, Andrew P.4 aut
700	1	a Oostra, Ben4 aut
700	1	a Pankow, James4 aut
700	1	a Petersen, Ann-Kristin4 aut
700	1	a Pramstaller, Peter P.4 aut
700	1	a Prokopenko, Inga4 aut
700	1	a Rathmann, Wolfgang4 aut
700	1	a Rayner, William4 aut
700	1	a Roden, Michael4 aut
700	1	a Rudan, Igor4 aut
700	1	a Rybin, Denis4 aut
700	1	a Scott, Laura J.4 aut
700	1	a Sigurdsson, Gunnar4 aut
700	1	a Sladek, Rob4 aut
700	1	a Thorleifsson, Gudmar4 aut
700	1	a Thorsteinsdottir, Unnur4 aut
700	1	a Tuomilehto, Jaakko4 aut
700	1	a Uitterlinden, Andre G.4 aut
700	1	a Vivequin, Sidonie4 aut
700	1	a Weedon, Michael N.4 aut
700	1	a Wright, Alan F.4 aut
700	1	a Hu, Frank B.4 aut
700	1	a Illig, Thomas4 aut
700	1	a Kao, Linda4 aut
700	1	a Meigs, James B.4 aut
700	1	a Wilson, James F.4 aut
700	1	a Stefansson, Kari4 aut
700	1	a van Duijn, Cornelia4 aut
700	1	a Altschuler, David4 aut
700	1	a Morris, Andrew D.4 aut
700	1	a Boehnke, Michael4 aut
700	1	a McCarthy, Mark I.4 aut
700	1	a Froguel, Philippe4 aut
700	1	a Palmer, Colin N. A.4 aut
700	1	a Wareham, Nicholas J.4 aut
700	1	a Groop, Leifu Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups4 aut0 (Swepub:lu)endo-lgr
700	1	a Frayling, Timothy M.4 aut
700	1	a Cauchi, Stephane4 aut
710	2	a Genomik, diabetes och endokrinologib Forskargrupper vid Lunds universitet4 org
773	0	t PLoS Geneticsd : Public Library of Science (PLoS)g 8:5q 8:5x 1553-7404
856	4	u https://portal.research.lu.se/files/1711683/3430914.pdfx primaryx freey FULLTEXT
856	4	u http://dx.doi.org/10.1371/journal.pgen.1002741x freey FULLTEXT
856	4	u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002741&type=printable
856	4 8	u https://lup.lub.lu.se/record/2895661
856	4 8	u https://doi.org/10.1371/journal.pgen.1002741

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Av författaren/redakt...: Perry, John R. B ...; Voight, Benjamin ...; Yengo, Loic; Amin, Najaf; Dupuis, Josee; Ganser, Martha; visa fler...; Grallert, Harald; Navarro, Pau; Li, Man; Qi, Lu; Steinthorsdottir ...; Scott, Robert A.; Almgren, Peter; Arking, Dan E.; Aulchenko, Yurii; Balkau, Beverley; Benediktsson, Ra ...; Bergman, Richard ...; Boerwinkle, Eric; Bonnycastle, Lor ...; Burtt, Noel P.; Campbell, Harry; Charpentier, Gui ...; Collins, Francis ...; Gieger, Christia ...; Green, Todd; Hadjadj, Samy; Hattersley, Andr ...; Herder, Christia ...; Hofman, Albert; Johnson, Andrew ...; Kottgen, Anna; Kraft, Peter; Labrune, Yann; Langenberg, Clau ...; Manning, Alisa K ...; Mohlke, Karen L.; Morris, Andrew P ...; Oostra, Ben; Pankow, James; Petersen, Ann-Kr ...; Pramstaller, Pet ...; Prokopenko, Inga; Rathmann, Wolfga ...; Rayner, William; Roden, Michael; Rudan, Igor; Rybin, Denis; Scott, Laura J.; Sigurdsson, Gunn ...; Sladek, Rob; Thorleifsson, Gu ...; Thorsteinsdottir ...; Tuomilehto, Jaak ...; Uitterlinden, An ...; Vivequin, Sidoni ...; Weedon, Michael ...; Wright, Alan F.; Hu, Frank B.; Illig, Thomas; Kao, Linda; Meigs, James B.; Wilson, James F.; Stefansson, Kari; van Duijn, Corne ...; Altschuler, Davi ...; Morris, Andrew D ...; Boehnke, Michael; McCarthy, Mark I ...; Froguel, Philipp ...; Palmer, Colin N. ...; Wareham, Nichola ...; Groop, Leif; Frayling, Timoth ...; Cauchi, Stephane; visa färre...

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