Abstract
We conducted a genome-wide linkage scan to detect loci that influence the levels of fasting triglycerides in plasma. Fasting triglyceride levels were available at 4 time points (visits), 2 pre- and 2 post-fenofibrate intervention. Multipoint identity-by-descent (MIBD) matrices were derived from genotypes using IBDLD. Variance-component linkage analyses were then conducted using SOLAR (Sequential Oligogenic Linkage Analysis Routines). We found evidence of linkage (logarithm of odds [LOD] ≥3) at 5 chromosomal regions with triglyceride levels in plasma. The highest LOD scores were observed for linkage to the estimated genetic value (additive genetic component) of the log-normalized triglyceride levels in plasma. Our results suggest that a chromosome 10 locus at 37 cM (LODpre = 3.01, LODpost = 3.72) influences fasting triglyceride levels in plasma regardless of the fenofibrate intervention, and that loci in chromosomes 1 at 170 cM and 4 at 24 cM ceases to affect the triglyceride levels when fenofibrate is present, while the regions in chromosomes 6 at 136 to 162 cM and 11 at 39 to 40 cM appear to influence triglyceride levels in response to fenofibrate.
Highlights
Triglyceride levels in plasma are highly heritable traits that have been consistently associated with obesity, cardiovascular disease, coronary heart disease, Type 2 diabetes, and metabolic disease
Data set We used real data from the GOLDN study that was made available to participants of the GAW20
The remaining 375,632 single-nucleotide polymorphism (SNP) were used in the estimation of Multipoint identity-by-descent (MIBD) at 3561 loci in our genetic map
Summary
Triglyceride levels in plasma are highly heritable traits that have been consistently associated with obesity, cardiovascular disease, coronary heart disease, Type 2 diabetes, and metabolic disease. The genetics of triglycerides has been the subject of extensive research, including both genome-wide association and genome-wide linkage studies in a variety of cohorts. Li et al [1] found linkage between serum triglyceride levels and chromosome 7 at 174 cM (7:174 cM, logarithm of odds [LOD] = 3.52) and suggestive linkage to 20:101 cM (LOD = 2.34), 13:111 cM (LOD = 2.00), and 9:104 cM (LOD = 1.90) in a sample of 1514 subjects from 320 obese white nuclear families. In a study of atherogenic dyslipidemia, Yu et al [2] reported linkage of triglyceride levels to 11:99 cM (LOD = 3.34) and 17:57 cM
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