ArticlePLoS genetics2012
Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02783469 (Genetics of Diabetes Audit and Research in Tayside Scotland), which is not on this map. Cited by 125 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetics of Diabetes Audit and Research in Tayside Scotland (DOLORisk Dundee)
Who cites it
125 citing papers in PubMed, 5 syntheses or guidelines pooled it, 267 citations in OpenAlex.
- Pooled it
- Modulation of genetic associations with serum urate levels by body-mass-index in humans.PloS one · 2015Pooled it
- Variants associated with type 2 diabetes identified by the transethnic meta-analysis study: assessment in American Indians and evidence for a new signal in LPP.Diabetologia · 2014Pooled it
- Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?Diabetologia · 2014Pooled it
- Genetic comorbidities in Parkinson's disease.Human molecular genetics · 2014Pooled it
- Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study.Nutrients · 2017Trial
- Trial
- Trial
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- Identification of genetic loci enriched in obese or lean T2D cases in the Korean population.Genes & genomics · 2025Article
- Parent-of-origin effects of phosphatidyl inositol-bisphosphate hydrolysis pathway genes on type 2 diabetes and the modification effect by obesity.Frontiers in endocrinology · 2025Article
- Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology.Communications medicine · 2024Article
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- Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.International journal of molecular sciences · 2024Article
- Stratified genome-wide association analysis of type 2 diabetes reveals subgroups with genetic and environmental heterogeneity.Human molecular genetics · 2023Article
- Global burden of type 2 diabetes attributable to non-high body mass index from 1990 to 2019.BMC public health · 2023Article
- Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight.Life (Basel, Switzerland) · 2023Article
- More than a Feeling: Dermatological Changes Impacted by Spaceflight.Research square · 2023Article
- Association between obesity and 1-year mortality in septic patients: a retrospective cohort study.BMJ open · 2023Article
- Being Underweight Is Associated with Increased Risk of Sudden Cardiac Death in People with Diabetes Mellitus.Journal of clinical medicine · 2023Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
78 authors at 20 institutions in 12 countries.
Funding
Abstract
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/m²) compared to obese cases (BMI≥30 Kg/m²). 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/m²) or 4,123 obese cases (BMI≥30 kg/m²), 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 = 8.4×10⁻⁹, 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 = 1.3×10⁻⁸, 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 = 3.2×10⁻¹⁴. This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2×10⁻¹⁶. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.