The Framingham Heart Study data were provided as Problem 1 of GAW13. The data consisted of family structure information, genotypic information (genome scan), and long-term phenotypic information for 1702 subjects from 330 families. Phenotypic information was provided over a period of 40 years for the parent generation and 20 years for the offspring generation. Phenotypic information consisted of values of repeated measurements of systolic blood pressure, height, weight, lipids (total plasma cholesterol, high density lipoprotein cholesterol, triglycerides), and fasting plasma glucose. We chose the phenotypes systolic blood pressure and body weight for our analysis.
Statistical analysis
Linear regression was perfomed using SAS [2] for the values of systolic blood pressure and body weight, at each time of examination, on age, for each individual separately. To obtain the values for adult life only, individuals younger than 18 years at the first examination were excluded. We omitted the values of these individuals instead of using the examinations with age 18 as a starting point because of lower reliability of the regression slopes (based on four time points at most and often less due to younger age and missing values) and because of their relatively low contribution due to small frequency (only 6% of individuals of Cohort 2 and none of Cohort 1 were younger than 18 years at their first examination). For systolic blood pressure, measurements were omitted if high blood pressure treatment was stated at this examination or any previous examination. The slope estimates were obtained for all individuals and used as a new phenotype providing a measure of the adult life change of systolic blood pressure and body weight. Further analyses of body weight change were conducted with regression slope up to an age of 50 as the phenotype "change up to 50" and with only those individuals who showed a positive weight slope (≥ 0.01), representing the phenotype adult life "body weight gain". Heritability estimates for the new phenotypes were obtained using variance-component methodology as implemented in the SOLAR package [3]. Heritability estimates were done analyzing the covariates sex, age at first examination and weight at first examination in addition. Only age at first examination contributed to the variance of the three phenotypes, explaining about 12% of the variance of "body weight change", 6% of the variance of "body weight gain", and 9% of the variance of "change up to 50". Because further examinations were at the same regular intervals for all individuals of the two cohorts, age at first examination represents age-dependence during the whole study. Two-point and multipoint quantitative trait linkage analyses were conducted on the regression slope estimates for adult life "body weight change", "body weight gain", and "change up to 50", using the SOLAR package. In the case of "body weight gain", we included age at first examination as a covariate. The information content of chromosomal regions with positive LOD scores was obtained using GENEHUNTER [4].