Segregation analysis of HDL cholesterol in the NHLBI family heart study and in Utah pedigrees

Florian Kronenberg, Hilary Coon, R. Curtis Ellison, Ingrid Borecki, Donna K. Arnett, Michael A. Province, John H. Eckfeldt, Paul N. Hopkins, Steven Hunt

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We investigated the genetic determination of high-density-lipoprotein cholesterol (HDL-C) levels in the NHLBI Family Heart Study by segregation analysis. Included was a total of 3755 subjects from 560 randomly selected nuclear families and 522 families selected due to a high family risk of coronary heart disease (CHD). In the whole dataset, there was no evidence for an allele at a major gene locus responsible for HDL-C levels lower than the population mean or even for significant bimodality for low levels of HDL-C. However, we observed evidence for a recessive allele that was associated with higher HDL-C levels than average. This evidence for a recessive major gene was independent of triglyceride concentrations and was most strongly observed in families recruited for CHD. The environmental model was rejected (P=0.0027) while the codominant and recessive models were not rejected (P=0.085 and P=0.133, respectively). The dominant model was also rejected (P<0.0001). In the recessive segregation model, the means of those inferred to be homozygous for the high HDL-C allele and those without the high HDL-C allele were separated by about 25 mg/dl HDL-C (73.9 ± 1.99 vs 48.2 ± 0.36 mg/dl). Because these results were unexpected, segregation was tested in a separate sample of 2013 individuals in 85 large pedigrees ascertained for early heart disease deaths, early stroke deaths, and early hypertension in Utah. Similar evidence for an allele at a major gene locus for high HDL-C was found. In summary, we did not find evidence for an allele at a major gene locus associated with low HDL-C levels segregating in pedigrees recruited for the NHLBI Family Heart Study, or in pedigrees ascertained in Utah for early CHD or related phenotypes. Instead we found some evidence for the segregation of an allele associated with high HDL-C.

Original languageEnglish
Pages (from-to)367-374
Number of pages8
JournalEuropean Journal of Human Genetics
Volume10
Issue number6
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
Pedigree
HDL Cholesterol
Alleles
Coronary Disease
Genes
Recessive Genes
Nuclear Family
LDL Cholesterol
Heart Diseases
Triglycerides
Stroke
Hypertension
Phenotype

Keywords

  • Atherosclerosis
  • Family heart study
  • Genetics
  • HDL cholesterol
  • Segregation analysis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Segregation analysis of HDL cholesterol in the NHLBI family heart study and in Utah pedigrees. / Kronenberg, Florian; Coon, Hilary; Ellison, R. Curtis; Borecki, Ingrid; Arnett, Donna K.; Province, Michael A.; Eckfeldt, John H.; Hopkins, Paul N.; Hunt, Steven.

In: European Journal of Human Genetics, Vol. 10, No. 6, 2002, p. 367-374.

Research output: Contribution to journalArticle

Kronenberg, F, Coon, H, Ellison, RC, Borecki, I, Arnett, DK, Province, MA, Eckfeldt, JH, Hopkins, PN & Hunt, S 2002, 'Segregation analysis of HDL cholesterol in the NHLBI family heart study and in Utah pedigrees', European Journal of Human Genetics, vol. 10, no. 6, pp. 367-374. https://doi.org/10.1038/sj.ejhg.5200818
Kronenberg, Florian ; Coon, Hilary ; Ellison, R. Curtis ; Borecki, Ingrid ; Arnett, Donna K. ; Province, Michael A. ; Eckfeldt, John H. ; Hopkins, Paul N. ; Hunt, Steven. / Segregation analysis of HDL cholesterol in the NHLBI family heart study and in Utah pedigrees. In: European Journal of Human Genetics. 2002 ; Vol. 10, No. 6. pp. 367-374.
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