Abstract
We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 +/- 0.14). Mean LDL particle size and small LDL particle concentration (-0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration. Our results suggest a significant genetic contribution to multiple lipoprotein subclasses studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration.
Highlights
We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans
We describe the genetic architecture of particle size and concentrations of VLDL, LDL, and HDL subclasses in the context of the Sea Islands Genetic African American Registry (Project SuGAR)
These estimates were computed after adjusting for gender, age, diabetes status, Body mass index (BMI), and whether the participants were on lipid-controlling medication, and range from 0.33 to 0.56
Summary
This study was conducted under Institutional Review Board approval from the Medical University of South Carolina, the University of Alabama at Birmingham (UAB), and Wake Forest University School of Medicine, and adhered to the tenets of the Declaration of Helsinki. Inclusion criteria included selfdescribed African-American race, at least one T2DM-affected sibling pair, no more than one of the parents affected with T2DM, and at least one parent still living. Probands and their parents were all born and raised in the South Carolina low country. The current genome scan involved a total of 967 individuals, including 791 T2DM-affected subjects and 176 unaffected relatives who were recruited from 418 families. The Project SuGAR registry includes 70 sib-pairs plus available parents, totaling 162 participants who were part of the Genetics of NonInsulin Dependent Diabetes (GENNID) study. Thirteen SNPs were removed from analyses because they violated Hardy-Weinberg assumptions (P < 0.0001)
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