Human Genetics

, Volume 111, Issue 3, pp 263–269

A genome-wide screen reveals evidence for a locus on chromosome 11 influencing variation in LDL cholesterol in the NHLBI Family Heart Study


  • Hilary Coon
    • Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA
  • John H. Eckfeldt
    • Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
  • Mark F. Leppert
    • Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA
  • Richard H. Myers
    • Section of Preventive Medicine and Epidemiology, Boston University, Framingham, Massachusetts, USA
  • Donna K. Arnett
    • Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
  • Gerardo Heiss
    • Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  • Michael A. Province
    • Division of Biostatistics, Washington University Medical School, St. Louis, Missouri, USA
  • Steven C. Hunt
    • Cardiovascular Genetics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
Original Investigation

DOI: 10.1007/s00439-002-0773-8

Cite this article as:
Coon, H., Eckfeldt, J.H., Leppert, M.F. et al. Hum Genet (2002) 111: 263. doi:10.1007/s00439-002-0773-8


A genome scan was performed for low-density lipoprotein cholesterol concentration (LDL-C) in white subjects who were ascertained through the NHLBI Family Heart Study (FHS). The NIH Mammalian Genotyping Service (Marshfield, Wis.) genotyped 401 autosomal markers spaced at approximate 10-cM intervals. Additional FHS families were genotyped by the FHS Molecular Laboratory at the University of Utah for 243 markers; 645 subjects were typed in both laboratories so that a combined map of the 644 markers from the two screening sets (average distance of 5.46 cM) could be produced. Analyses were done on 2,799 genotyped subjects in 500 families where at least two genotyped persons in the family had measured LDL-C levels (average number of genotyped family members=5.95). The variance components method was used as implemented in GeneHunter (Kruglyak et al. 1996). Prior to analysis, each phenotype was adjusted, within sex, for age, age squared, body mass index, waist-hip ratio, alcohol, smoking, medication status for diabetes and hypertension, estrogen use, and field center location. Linkage analyses were performed, first excluding 305 subjects on lipid-lowering medications, then again including the data from these subjects. The highest peak was on chromosome 11 at 56.3–56.4 cM, with a maximum lod score of 3.72. Two genome scans of lipid traits in other populations have found peaks in this region. Other scores at or above 1.9 occurred on chromosomes 5 (lod=1.89 at 1.6 cM), 10 (lod=2.47 at 127.1 cM), 17 (lod=2.33 at 116.3 cM), and 21 (lod=2.74 at 45.2 cM).

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© Springer-Verlag 2002