Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by homozygosity-by-descent mapping in a large Hutterite pedigree

Serum triglyceride (TG) level is a well-known risk factor for cardiovascular disease, a leading cause of morbidity and mortality in Western countries. Although genome-wide scans for TG have been conducted in several populations, few loci have shown strong evidence for linkage. The Hutterites are a founder population, which practices a communal lifestyle that includes a uniformly high-fat, high-cholesterol diet. We measured serum TG in 485 Hutterites >or=14 years old and performed a genome-wide scan to find genetic determinants of the observed variation in TG levels, using mapping methods that take advantage of the extensive inbreeding and linkage disequilibrium (LD) in this single, 1623-member pedigree. We report two highly significant associations with TG levels, alleles at D2S410 on 2q14 (locus P=5.8 x 10(-6), genome-wide P=0.005) and at IFNA on chromosome 9p21 (locus P=4.3 x 10(-5), genome-wide P=0.024). In each case, homozygosity at the locus is associated with low TG levels, suggesting that alleles at nearby loci may protect against high TG levels.