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Stratifying Type 2 ...
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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Perry, John R. B. (author)
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Voight, Benjamin F. (author)
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Yengo, Loic (author)
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show more...
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Amin, Najaf (author)
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Dupuis, Josee (author)
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Ganser, Martha (author)
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Grallert, Harald (author)
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Navarro, Pau (author)
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Li, Man (author)
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Qi, Lu (author)
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Steinthorsdottir, Valgerdur (author)
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Scott, Robert A. (author)
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- Almgren, Peter (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Arking, Dan E. (author)
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Aulchenko, Yurii (author)
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Balkau, Beverley (author)
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Benediktsson, Rafn (author)
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Bergman, Richard N. (author)
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Boerwinkle, Eric (author)
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Bonnycastle, Lori (author)
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Burtt, Noel P. (author)
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Campbell, Harry (author)
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Charpentier, Guillaume (author)
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Collins, Francis S. (author)
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Gieger, Christian (author)
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Green, Todd (author)
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Hadjadj, Samy (author)
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Hattersley, Andrew T. (author)
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Herder, Christian (author)
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Hofman, Albert (author)
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Johnson, Andrew D. (author)
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Kottgen, Anna (author)
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Kraft, Peter (author)
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Labrune, Yann (author)
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Langenberg, Claudia (author)
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Manning, Alisa K. (author)
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Mohlke, Karen L. (author)
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Morris, Andrew P. (author)
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Oostra, Ben (author)
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Pankow, James (author)
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Petersen, Ann-Kristin (author)
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Pramstaller, Peter P. (author)
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Prokopenko, Inga (author)
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Rathmann, Wolfgang (author)
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Rayner, William (author)
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Roden, Michael (author)
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Rudan, Igor (author)
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Rybin, Denis (author)
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Scott, Laura J. (author)
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Sigurdsson, Gunnar (author)
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Sladek, Rob (author)
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Thorleifsson, Gudmar (author)
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Thorsteinsdottir, Unnur (author)
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Tuomilehto, Jaakko (author)
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Uitterlinden, Andre G. (author)
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Vivequin, Sidonie (author)
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Weedon, Michael N. (author)
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Wright, Alan F. (author)
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Hu, Frank B. (author)
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Illig, Thomas (author)
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Kao, Linda (author)
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Meigs, James B. (author)
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Wilson, James F. (author)
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Stefansson, Kari (author)
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van Duijn, Cornelia (author)
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Altschuler, David (author)
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Morris, Andrew D. (author)
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Boehnke, Michael (author)
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McCarthy, Mark I. (author)
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Froguel, Philippe (author)
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Palmer, Colin N. A. (author)
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Wareham, Nicholas J. (author)
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Frayling, Timothy M. (author)
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Cauchi, Stephane (author)
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(creator_code:org_t)
- 2012-05-31
- 2012
- English.
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:5
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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Perry, John R. B ...
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Voight, Benjamin ...
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Yengo, Loic
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Amin, Najaf
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Dupuis, Josee
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Ganser, Martha
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show more...
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Grallert, Harald
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Navarro, Pau
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Li, Man
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Qi, Lu
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Steinthorsdottir ...
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Scott, Robert A.
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Almgren, Peter
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Arking, Dan E.
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Aulchenko, Yurii
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Balkau, Beverley
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Benediktsson, Ra ...
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Bergman, Richard ...
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Boerwinkle, Eric
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Bonnycastle, Lor ...
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Burtt, Noel P.
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Campbell, Harry
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Charpentier, Gui ...
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Collins, Francis ...
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Gieger, Christia ...
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Green, Todd
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Hadjadj, Samy
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Hattersley, Andr ...
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Herder, Christia ...
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Hofman, Albert
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Johnson, Andrew ...
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Kottgen, Anna
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Kraft, Peter
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Labrune, Yann
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Langenberg, Clau ...
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Manning, Alisa K ...
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Mohlke, Karen L.
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Morris, Andrew P ...
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Oostra, Ben
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Pankow, James
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Petersen, Ann-Kr ...
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Pramstaller, Pet ...
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Prokopenko, Inga
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Rathmann, Wolfga ...
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Rayner, William
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Roden, Michael
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Rudan, Igor
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Rybin, Denis
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Scott, Laura J.
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Sigurdsson, Gunn ...
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Sladek, Rob
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Thorleifsson, Gu ...
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Thorsteinsdottir ...
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Tuomilehto, Jaak ...
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Uitterlinden, An ...
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Vivequin, Sidoni ...
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Weedon, Michael ...
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Wright, Alan F.
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Hu, Frank B.
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Illig, Thomas
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Kao, Linda
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Meigs, James B.
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Wilson, James F.
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Stefansson, Kari
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van Duijn, Corne ...
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Altschuler, Davi ...
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Morris, Andrew D ...
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Boehnke, Michael
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McCarthy, Mark I ...
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Froguel, Philipp ...
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Palmer, Colin N. ...
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Wareham, Nichola ...
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Groop, Leif
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Frayling, Timoth ...
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Cauchi, Stephane
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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 ...
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PLoS Genetics
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Lund University