Journal
PLOS GENETICS
Volume 8, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002741
Keywords
-
Categories
Funding
- Wellcome Trust [092447/Z/10/Z, 083270/Z/07/Z]
- MRC [G0601261]
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, DK062370, DK072193, UL1RR025005, NIDCR: U01DE018993, U01DE018903, NIAAA: U10AA008401, NIDA: P01CA089392, R01DA013423, NCI: CA63464, CA54281, CA136792, Z01CP010200]
- NIH Roadmap for Medical Research
- Swedish Research Council
- NHS Research and Development
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
- Boston Medical Center
- National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, K24 DK080140]
- European Community [HEALTH-F4-2007-201413]
- French Government (Agence Nationale de la Recherche)
- French Region of Nord Pas De Calais (Contrat de Projets Etat-Region)
- French Ministry of Health
- Association Francaise des Diabetiques
- Programme National de Recherche sur le Diabete
- Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques
- Association Diabete Risque Vasculaire (Paris, France)
- Groupe d'Etude des Maladies Metaboliques et Systemiques
- European Union of European Community [LSHM-CT-2006-518153]
- Caisse Nationale d'Assurance Maladie des Travailleurs Salaries
- Lilly
- Novartis Pharma
- Sanofi-Aventis
- Institut National de la Sante et de la Recherche Medicale (INSERM) (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR)
- Association Diabete Risque Vasculaire
- Federation Francaise de Cardiologie
- Fondation de France
- Office National Interprofessionnel des Vins
- Ardix Medical
- Bayer Diagnostics
- Becton Dickinson
- Cardionics
- Merck Sante
- Novo Nordisk
- Pierre Fabre
- Roche and Topcon
- NIH Genes, Environment and Health Initiative (GEI) [U01HG004402, U01HG004399, U01HG004738, U01HG004422, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033]
- European Union [LSHG-CT-2006-018947]
- NWO
- Erasmus MC
- Centre for Medical Systems Biology (CMSB)
- Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano
- South Tyrolean Sparkasse Foundation
- Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]
- Medical Research Council UK
- German Center for Diabetes Research (DZD)
- Helmholtz Zentrum Munchen, Neuherberg, Germany
- German Federal Ministry of Education and Research the Federal Ministry of Health
- Ministry of Innovation, Science, Research, and Technology of the state North Rhine-Westphalia
- German National Genome Research Network (NGFN)
- Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
- Wellcome Trust [092447/Z/10/Z] Funding Source: Wellcome Trust
- MRC [MC_U127592696, MC_U127561128, G0601261, MC_PC_U127592696, MC_PC_U127561128] Funding Source: UKRI
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [MC_U127561128, G0601261, MC_U127592696, MC_PC_U127561128, MC_PC_U127592696, MC_U106179471] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available