Insulin clearance: confirmation as a highly heritable trait, and genome-wide linkage analysis.

Diabetologia
Xiuqing GuoMark O Goodarzi

Abstract

We have previously documented a high heritability of insulin clearance in a Hispanic cohort. Here, our goal was to confirm the high heritability in a second cohort and search for genetic loci contributing to insulin clearance. Hyperinsulinaemic-euglycaemic clamps were performed in 513 participants from 140 Hispanic families. Heritability was estimated for clamp-derived insulin clearance and a two-phase genome-wide linkage scan was conducted using a variance components approach. Linkage peaks were further investigated by candidate gene association analysis in two cohorts. The covariate-adjusted heritability of insulin clearance was 73%, indicating that the majority of the phenotypic variance is due to genetic factors. In the Phase 1 linkage scan, no signals with a logarithm of odds (LOD) score >2 were detected. In the Phase 2 scan, two linkage peaks with an LOD >2 for insulin clearance were identified on chromosomes 15 (LOD 3.62) and 20 (LOD 2.43). These loci harbour several promising candidate genes for insulin clearance, with 12 single nucleotide polymorphisms (SNPs) on chromosome 15 and six SNPs on chromosome 20 being associated with insulin clearance in both Hispanic cohorts. In a second Hispanic cohort, we confirmed that in...Continue Reading

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Citations

Dec 23, 2014·Endocrine Research·Ladislav DedikAdela Penesova
Jul 19, 2018·Diabetes, Obesity & Metabolism·Francesca PiccininiRichard N Bergman
Sep 19, 2019·Journal of the Endocrine Society·Dylan D ThomasCaroline M Apovian
Feb 14, 2020·The Journal of Clinical Endocrinology and Metabolism·Andin FosamRanganath Muniyappa
Sep 25, 2017·The Journal of Clinical Endocrinology and Metabolism·Worapaka ManosroiEllen W Seely
Nov 15, 2017·Acta Diabetologica·Chinmay S MaratheMichael Horowitz
Feb 26, 2021·Metabolism: Clinical and Experimental·Diego O BorgesM Paula Macedo
Mar 7, 2021·International Journal of Molecular Sciences·Malcolm A LeissringGermán Perdomo
Aug 8, 2021·International Journal of Molecular Sciences·Joseph A M J L Janssen

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