Systematic Heritability and Heritability Enrichment Analysis for Diabetes Complications in UK Biobank and ACCORD Studies
figure
posted on 2022-02-08, 16:02 authored by Juhyun Kim, Aubrey Jensen, Seyoon Ko, Sridharan Raghavan, Lawrence S. Phillips, Adriana Hung, Yan Sun, Hua Zhou, Peter Reaven, Jin J. ZhouDiabetes-related
complications reflect longstanding damage to small and large vessels throughout
the body. In addition to the duration of diabetes and poor glycemic control,
genetic factors are important contributors to the variability in the
development of vascular complications. Early heritability studies found strong
familial clustering of both macrovascular and microvascular complications.
However, they were limited by small sample sizes and large phenotypic
heterogeneity, leading to less accurate estimates. We take advantage of two independent
studies—UK Biobank and the Action to Control Cardiovascular Risk in Diabetes
trial to survey the SNP-heritability for diabetes microvascular (diabetic
kidney disease and diabetic retinopathy) and macrovascular (cardiovascular
events) complications. Heritability for diabetic kidney disease was estimated
at 29%. Heritability estimates for microalbuminuria ranged from 24% to 60% and
was 41% for macroalbuminuria. Heritability estimates of diabetic retinopathy
ranged from 6% to 33%, depending on the phenotype definition. More severe
diabetes retinopathy possessed higher genetic contributions. We show, for the
first time, that rare variants account for much of the heritability of diabetic
retinopathy. This study suggests that a large portion of the genetic risk of diabetes
complications is yet to be discovered and emphasizes the need for additional
genetic studies of diabetes complications.