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

• Published in: Human molecular genetics Vol. 12; no. 2; pp. 137 - 144
• Main Authors: Newman, Dina L., Abney, Mark, Dytch, Harvey, Parry, Rodney, McPeek, Mary Sara, Ober, Carole
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.01.2003; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular Diseases - blood; Cardiovascular Diseases - genetics; Chromosome Mapping; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 9; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Ethnic Groups; European Continental Ancestry Group; Founder Effect; Genome, Human; Humans; Linkage Disequilibrium - genetics; Medical sciences; Middle Aged; Obesity - blood; Obesity - genetics; Pedigree; Triglycerides - blood; Genetic mapping; Human; Linkage; Chromosome 9; Cardiovascular disease; Population; Serum; Locus; Triglyceride; Chromosome 2; Genetic determinism; Quantitative analysis
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddg012

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 ≥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=5.8×10−6, genome-wide P=0.005) and at IFNA on chromosome 9p21 (locus P=4.3×10−5, 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.