A genome-wide linkage scan identifies multiple chromosomal regions influencing serum lipid levels in the population on the Samoan islands

Karolina Åberg,Feng Dai,Guangyun Sun,Ember Keighley,Subba Rao Indugula,Linda Bausserman,Satupaitea Viali,John Tuitele,Ranjan Deka,Daniel E Weeks,Stephen T Mcgarvey

doi:10.1194/jlr.m800194-jlr200

Abstract

Abnormal lipid levels are important risk factors for cardiovascular diseases. We conducted genome-wide variance component linkage analyses to search for loci influencing total cholesterol (TC), LDL, HDL and triglyceride in families residing in American Samoa and Samoa as well as in a combined sample from the two polities. We adjusted the traits for a number of environmental covariates, such as smoking, alcohol consumption, physical activity, and material lifestyle. We found suggestive univariate linkage with log of the odds (LOD) scores > 3 for LDL on 6p21-p12 (LOD 3.13) in Samoa and on 12q21-q23 (LOD 3.07) in American Samoa. Furthermore, in American Samoa on 12q21, we detected genome-wide linkage (LOD(eq) 3.38) to the bivariate trait TC-LDL. Telomeric of this region, on 12q24, we found suggestive bivariate linkage to TC-HDL (LOD(eq) 3.22) in the combined study sample. In addition, we detected suggestive univariate linkage (LOD 1.9-2.93) on chromosomes 4p-q, 6p, 7q, 9q, 11q, 12q 13q, 15q, 16p, 18q, 19p, 19q and Xq23 and suggestive bivariate linkage (LOD(eq) 2.05-2.62) on chromosomes 6p, 7q, 12p, 12q, and 19p-q. In conclusion, chromosome 6p and 12q may host promising susceptibility loci influencing lipid levels; however, the low degree of overlap between the three study samples strongly encourages further studies of the lipid-related traits.

Highlights

The broad region on 12q21-qtel hosts multiple linkage signals (LOD 5 1.96–2.26) for total cholesterol (TC) in American Samoa and in the combined study sample (Fig. 1, right column)
We investigate the serum lipid profile, including total cholesterol (TC), LDL, HDL, and triglyceride (TG), in the combined study sample and in the polityspecific study samples from the Samoan islands
On chromosome 7q, where bivariate linkage was detected to TC-LDL in American Samoa, both complete pleiotropy and coincident linkage could be rejected, suggesting that some but not complete pleiotropy occurs in this region

Summary

Introduction

The broad region on 12q21-qtel hosts multiple linkage signals (LOD 5 1.96–2.26) for TC in American Samoa and in the combined study sample (Fig. 1, right column). The only signal with suggestive linkage for HDL was detected on chromosome 15q14 (LOD 5 1.96, LODmtc 5 1.66) in the Samoa sample set (Table 3).

Results

Conclusion