It is proposed to examine in previously collected data sets from nine United States populations patterns of familial similarity and gene-environment interactions by a new statistical methodology, Structured Exploratory Data Analysis (SEDA). The data to be analyzed include physiologic variables of blood pressure, plasma lipid and lipoprotein cholesterol concentrations and weight, and a variety of cultural and environmental variables including diet, stress, physical activity, smoking behavior, and measures of knowledge, attitude and opinions that relate to heart disease, surveyed in unrelated individuals, spouse-pairs, and nuclear family sets. Among the issues to be examined are the effects of parental interaction, sibship interaction, common family environment, parent-offspring transmission, mode of inheritance, characteristics of the trait distribution, population heterogeneity, generational differences, family structure, and population structure on familial interactions. In addition, to investigate gene-environment interactions we propose to employ a hierarchy of stratifications and weighting procedures that contrast the effect of different levels of one or more environmental factors on SEDA mode of inheritance statistics.
Other specific aims are to compare familial similarity patterns and gene-environment interactions: (1) across geographically diverse populations, (ii) between randomly selected families and families ascertained via a high lipid proband, and (iii) in families measured repeatedly over time. Our objective is to distinguish the relative strengths and forms of various influences that affect the familial aggregation of cardiovascular risk factors for the purpose of eventually offering strategies to most effectively approach their modification. Four classes of SEDA-statistics are to be examined: SEDA-functionals, SEDA-indices, association arrays, and various weightings and stratifications of the SEDA-functionals and SEDA-indices. Multivariate extensions of all four classes of statistics will be studied. The significance of these SEDA-statistics will be determined by a spectrum of permutation techniques that selectively shuffle the trait values across families. The process systematically alters certain family structure relationships while keeping other familial relationships intact.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030856-03
Application #
3341875
Study Section
Epidemiology and Disease Control Subcommittee 3 (EDC)
Project Start
1984-06-01
Project End
1988-05-31
Budget Start
1986-06-01
Budget End
1988-05-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Karlin, S; Blaisdell, B E; Mocarski, E S et al. (1989) A method to identify distinctive charge configurations in protein sequences, with application to human herpesvirus polypeptides. J Mol Biol 205:165-77
Blaisdell, B E; Karlin, S (1988) Distinctive charge configurations in proteins of the Epstein-Barr virus and possible functions. Proc Natl Acad Sci U S A 85:6637-41
Williams, P T; Fortmann, S P; Terry, R B et al. (1987) Associations of dietary fat, regional adiposity, and blood pressure in men. JAMA 257:3251-6
Karlin, S; Blaisdell, B E (1987) A model for the development of the tandem repeat units in the EBV ori-P region and a discussion of their possible function. J Mol Evol 25:215-29
Williams, P T; Karlin, S; Farquhar, J W (1987) Permutation analyses of familial association arrays for lipoprotein concentrations in families of the Stanford Five City Project. Am J Epidemiol 126:1126-40
Karlin, S (1986) Significant potential secondary structures in the Epstein-Barr virus genome. Proc Natl Acad Sci U S A 83:6915-9
Williams, P T; Krauss, R M; Kindel-Joyce, S et al. (1986) Relationship of dietary fat, protein, cholesterol, and fiber intake to atherogenic lipoproteins in men. Am J Clin Nutr 44:788-97
Karlin, S; Williams, P T; Carmelli, D et al. (1985) Permutation methods for the structured exploratory data analysis (SEDA) of total cholesterol measured in five Israeli populations. Am J Epidemiol 122:163-86
Karlin, S; Ghandour, G (1985) DNA sequence patterns in human, mouse, and rabbit immunoglobulin kappa-genes. J Mol Evol 22:195-208
Karlin, S; Ghandour, G (1985) The use of multiple alphabets in kappa-gene immunoglobulin DNA sequence comparisons. EMBO J 4:1217-23

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