The proposed research develops and applies appropriate methodology for the detection of major loci and the resolution of genetic and familial environmental effects on several phenotypes of importance to coronary heart disease (CHD), including plasma lipids and lipoprotein concentrations. Family data collected at five of the Lipid Research Clinics (LRCs) established by the National Heart, Lung, and Blood Institute (NHLBI) will be analyzed. New statistical methods will be developed for the families ascertained through probands with elevated lipid levels (non-random samples), and analyses will be performed on all data in a unified manner. Modes of inheritance will be investigated for two familial dyslipoproteinemias of considerable clinical significance: familial combined hyperlipidemia and familial primary hypoalphalipoproteinemia, two conditions known to be associated with premature CHD. Using both randomly and non-randomly ascertained data, we will especially investigate the possible major gene effects on these conditions. Specific hypotheses will be formulated and tested on the cultural and biological effects, heterogeneity among the LRCs (identifying the specific sources of such heterogeneity), familial basis for associations among the multiple risk factors, and temporal trends in family resemblance (i.e., age-dependent variation in heritabilities). They will be formulated using appropriate path models. The proposed research is expected to improve significantly our knowledge of the familial associations and interactions among the phenotypes, and to provide a systematic assessment of the familial environmental effects in diverse populations. The two unique features of this proposal are the innovative handling of both the random and non-random samples of family data, and the use of state-of-the-art models and statistical methods. It should be clarified that this proposal only complements, and does not duplicate, the ongoing efforts at the Central Patient Registry and Coordinating Center for the LRCs in Chapel Hill. It is believed that this cost-effective Public Health Research will expand understanding of a huge, expensive, resourceful, and previously collected data set.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033973-03
Application #
3346440
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-07-07
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Province, M A; Rao, D C (1995) General purpose model and a computer program for combined segregation and path analysis (SEGPATH): automatically creating computer programs from symbolic language model specifications. Genet Epidemiol 12:203-19
Sprecher, D L; Feigelson, H S; Laskarzewski, P M (1993) The low HDL cholesterol/high triglyceride trait. Arterioscler Thromb 13:495-504
Nirmala, A; Mitchell, L E; Rice, T et al. (1993) Assessment of adiposity in an Indian population: familial correlations. Genet Epidemiol 10:133-43
Rice, T; Nirmala, A; Reddy, P C et al. (1992) Familial resemblance of blood pressure with residual household environmental effects in consanguineous and nonconsanguineous families from Andhra Pradesh, India. Hum Biol 64:869-89
Rice, T; Laskarzewski, P M; Rao, D C (1992) Commingling and complex segregation analysis of fasting plasma glucose in the Lipid Research Clinics family study. Am J Med Genet 44:399-404
Rice, T; Laskarzewski, P M; Perry, T S et al. (1992) Commingling and segregation analysis of serum uric acid in five North American populations: the Lipid Research Clinics family study. Hum Genet 90:133-8
Rice, T; Vogler, G P; Laskarzewski, P M et al. (1991) Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. Hum Biol 63:419-39
Rice, T; Vogler, G P; Laskarzewski, P M et al. (1991) Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study. Am J Med Genet 39:270-7
Borecki, I B; Rice, T; Bouchard, C et al. (1991) Commingling analysis of generalized body mass and composition measures: the Quebec Family Study. Int J Obes 15:763-73

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