Abstract
Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.
Highlights
Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisting disorders and major components of metabolic syndrome that cause a substantial public health and economic burden worldwide. Susceptibility to such complex diseases is strongly influenced by multiple genetic factors combined with environmental factors, and all these diseases are further characterized by a chronic inflammatory process
Evidence has showed that some loci confer risk for more than one of the studied diseases, and most common diseases arise from interaction between multiple genetic variations
The common genetic basis for 2DM and obesity has been indicated, with the common obesity genes being found through 2DM studies [3]
Summary
Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisting disorders and major components of metabolic syndrome that cause a substantial public health and economic burden worldwide. Susceptibility to such complex diseases is strongly influenced by multiple genetic factors combined with environmental factors, and all these diseases are further characterized by a chronic inflammatory process. The strong genetic basis has been successfully revealed for evidence has showed that some loci confer risk for more than one of the studied diseases, and most common diseases arise from interaction between multiple genetic variations. These data indicates the potentially strong common genetic aspects among 2DM, obesity and CAD
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