Genometric Analysis of Quantitative Traits

Human Genome Research

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Abstract

This project now replaces projects HG000103, HG000128, HG000201, HG000202, HG000204, HG000205, HG000307 and HG000308. Although each of these original projects focused on different quantitative traits (e.g., obesity, diabetes, asthma, CLSD) all were applications of statistical genetic analysis of quantitative traits. All of the original projects involved linkage and/or tests of association in an attempt to identify genetic components that may be, at least in part, responsible for the variation seen in the trait. Obesity As part of an ongoing study of traits related to obesity in the Old-Order Amish, seven two- and three-generation families were assessed for twenty-one obesity related traits and genotyped. Linkage analysis and intra-familial tests of association strongly suggest a candidate region flanked by markers D7S1804 and D7S3070 for BMI. This region contains a large proportion of genes related to olfactory and taste receptors. Cardiovascular Disease The data consist of 717 observations (87 pedigrees) from Korea. The families were ascertained through probands undergoing elective coronary arteriography as part of the Yonsei Coronary Artery Disease Study. Age, sex, cigarette smoking, alcohol consumption among others covariates were obtained through a questionnaire. The following traits were measured: BMI levels of hemostatic factors (clotting factors VII and fibrinogen and plasminogen activator inhibitor ? 1 or PAI-1), triglycerides, total and HDL cholesterol, and blood pressure. The individual and family identification numbers were randomized before analysis to respect confidentiality. The Regression of Offspring on Mid-Parent (ROMP) method was used to estimate overall trait heritability and locus-specific heritability, and to test for association between the traits and the candidate polymorphisms. Although significant associations were found, these polymorphisms account for only a small percentage of the heritability of the traits (3-7%). This suggests that several other genes and/or shared familial and environmental factors may be responsible for the high heritability of these traits. Diabetes Type 2 diabetes or NIDDM is a multifactorial disorder affecting an estimated 8.6 million Americans over age 60. Dr. Richard Havlik (NIA) and other collaborators provided genetic marker data from these potential candidate regions, in an independent sample comprising 175 Japanese-American families from the Hawaiian population with a high prevalence of diabetes. Evidence of both linkage and association was obtained in the candidate region on chromosome 14, constituting independent replication of previous results in this region. These results provide additional support for the hypothesis that a susceptibility locus for Type 2 diabetes may reside in this candidate region on chromosome 14. Statistical analyses of DNA markers in this candidate region using the expression level of adiponectin, a protein related to obesity and type-2 diabetes, has been completed.