Emma Dahlström1,2,3, Niina Sandholm4,5,6. 1. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Haartmaninkatu 8, 00290, Helsinki, Finland. 2. Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3. Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 4. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Haartmaninkatu 8, 00290, Helsinki, Finland. niina.sandholm@helsinki.fi. 5. Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. niina.sandholm@helsinki.fi. 6. Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. niina.sandholm@helsinki.fi.
Abstract
PURPOSE OF REVIEW: Diabetic complications affecting the kidneys, retina, nerves, and the cardiovasculature are the major causes of morbidity and mortality in diabetes. This paper aims to review the current understanding of the genetic basis of these complications, based on recent findings especially from genome-wide association studies. RECENT FINDINGS: Variants in or near AFF3, RGMA-MCTP2, SP3-CDCA7, GLRA3, CNKSR3, and UMOD have reached genome-wide significance (p value <5 × 10-8) for association with diabetic kidney disease, and recently, GRB2 was reported to be associated at genome-wide significance with diabetic retinopathy. While some loci affecting cardiovascular disease in the general population have been replicated in diabetes, GLUL affects the risk of cardiovascular disease specifically in diabetic subjects. Genetic findings are emerging for diabetic complications, although the studies remain relatively small compared to those for type 1 and type 2 diabetes. In addition to pinpointing specific loci, the studies also reveal biological information on correlated traits and pathways.
PURPOSE OF REVIEW: Diabetic complications affecting the kidneys, retina, nerves, and the cardiovasculature are the major causes of morbidity and mortality in diabetes. This paper aims to review the current understanding of the genetic basis of these complications, based on recent findings especially from genome-wide association studies. RECENT FINDINGS: Variants in or near AFF3, RGMA-MCTP2, SP3-CDCA7, GLRA3, CNKSR3, and UMOD have reached genome-wide significance (p value <5 × 10-8) for association with diabetic kidney disease, and recently, GRB2 was reported to be associated at genome-wide significance with diabetic retinopathy. While some loci affecting cardiovascular disease in the general population have been replicated in diabetes, GLUL affects the risk of cardiovascular disease specifically in diabetic subjects. Genetic findings are emerging for diabetic complications, although the studies remain relatively small compared to those for type 1 and type 2 diabetes. In addition to pinpointing specific loci, the studies also reveal biological information on correlated traits and pathways.
Entities:
Keywords:
Cardiovascular disease; Diabetic complications; Diabetic retinopathy; End-stage renal disease; Genetic risk factors; Genome-wide association study
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