ArticlePLoS genetics2010
Use of genome-wide expression data to mine the "Gray Zone" of GWA studies leads to novel candidate obesity genes.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 0 citations in OpenAlex.
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- F13A1 transglutaminase expression in human adipose tissue increases in acquired excess weight and associates with inflammatory status of adipocytes.International journal of obesity (2005) · 2021Article
- Factor XIII-A in Diseases: Role Beyond Blood Coagulation.International journal of molecular sciences · 2021Review
- An Integrative Analysis of Transcriptome and GWAS Data to Identify Potential Candidate Genes Influencing Meat Quality Traits in Pigs.Frontiers in genetics · 2021Article
- Transglutaminases and Obesity in Humans: Association ofInternational journal of molecular sciences · 2020Article
- Factor XIIIa inhibitors as potential novel drugs for venous thromboembolism.European journal of medicinal chemistry · 2020Review
- Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study.Genes and immunity · 2020Article
- Gene co-expression analysis for functional classification and gene-disease predictions.Briefings in bioinformatics · 2018Article
- Full genetic analysis for genome-wide association study of Fangji: a powerful approach for effectively dissecting the molecular architecture of personalized traditional Chinese medicine.Acta pharmacologica Sinica · 2018Review
- Obesity and Brain Positron Emission Tomography.Nuclear medicine and molecular imaging · 2018Review
- Thrombin promotes diet-induced obesity through fibrin-driven inflammation.The Journal of clinical investigation · 2017Article
- Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA).Environmental health : a global access science source · 2016Article
- Factor XIII-A transglutaminase deficient mice show signs of metabolically healthy obesity on high fat diet.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
Abstract
To get beyond the "low-hanging fruits" so far identified by genome-wide association (GWA) studies, new methods must be developed in order to discover the numerous remaining genes that estimates of heritability indicate should be contributing to complex human phenotypes, such as obesity. Here we describe a novel integrative method for complex disease gene identification utilizing both genome-wide transcript profiling of adipose tissue samples and consequent analysis of genome-wide association data generated in large SNP scans. We infer causality of genes with obesity by employing a unique set of monozygotic twin pairs discordant for BMI (n = 13 pairs, age 24-28 years, 15.4 kg mean weight difference) and contrast the transcript profiles with those from a larger sample of non-related adult individuals (N = 77). Using this approach, we were able to identify 27 genes with possibly causal roles in determining the degree of human adiposity. Testing for association of SNP variants in these 27 genes in the population samples of the large ENGAGE consortium (N = 21,000) revealed a significant deviation of P-values from the expected (P = 4x10(-4)). A total of 13 genes contained SNPs nominally associated with BMI. The top finding was blood coagulation factor F13A1 identified as a novel obesity gene also replicated in a second GWA set of approximately 2,000 individuals. This study presents a new approach to utilizing gene expression studies for informing choice of candidate genes for complex human phenotypes, such as obesity.
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