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A genome-wide scan was performed in a randomly ascertained set of 330 extended families from the population-based Framingham Study to identify chromosomal regions possibly linked to bone mineral density (BMD). A set of 401 microsatellite markers was typed at a 10-centimorgan (cM) average density throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and vitamin D intakes, smoking, physical activity, and estrogen use in women within each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were found for the adjusted BMD at all sites. Two-point and multipoint quantitative linkage analyses were performed for each BMD site using the maximum likelihood variance components method. By two-point screening, loci of suggestive linkage were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395 (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of trochanteric BMD at a broad (approximately 20 cM) interval on chromosome 21q, with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at 8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest genome screen to date for genes underlying normal variation in BMD, adjusted for a large number of covariates, will help to identify new positional candidate genes, otherwise unrecognized.

The proportion of deaths attributed to suicide was examined among 506 deceased individuals with diagnosed or suspected Huntington's Disease from New England USA. Comparison of this proportion with that of the general population indicated that the odds of a death being due to suicide in the Huntington's disease group is 8.2 times that of the Massachusetts population for persons aged 50 to 69 yr, but no difference appears in the 10 to 49 yr age group. Among the 157 Huntington's disease patients for whom cause of death was known, the corresponding odds estimates are 23.0 for the 50 to 69 yr age group and 2.7 for the 10 to 49 yr age group. More than half of the suicides occurred in individuals who showed early signs of the illness but who had not been diagnosed, suggesting that suicide may occur more frequently in the early stages of the illness.

The advent of presymptomatic and prenatal testing in Huntington disease (HD) may change the reproductive behavior of persons at risk for HD. In order to assess future change, an analysis of fertility and reproductive fitness was carried out on 999 affected and 2,253 unaffected offspring from 235 New England families. Ascertainment biases observed for persons born before 1910 and after 1929 reduced the sample to 250 HD cases and 201 unaffected sib controls born between 1910 and 1929. No increase in reproductive rate was found in HD-affected men compared to male control sibs. A small increase in fertility averaging 0.5 child was seen in HD-affected females compared to unaffected females, but this difference was not significant. The increase in mean number of children for HD females is accounted for in part by a small number of affected women who had very large families. No evidence was found to suggest that any increase in reproductive rate for affected persons was related to offspring being born after HD onset. The fitness of both HD-affected and unaffected females was not significantly different from that of the general population of Massachusetts.

Data from the Framingham Study, a population-based prospective study of 5,209 persons, were analyzed to determine whether a parental history of death by coronary artery disease (CAD) before or after 65 years of age was an independent risk factor for CAD of early onset (age younger than 60 years) or late onset (age 60 years or older) among the men and women in the cohort. Death due to CAD in parents was associated with a 30% increase in the risk of CAD. The effect was apparently stronger for an early CAD outcome, with adjusted relative risks of 1.5 for early and 1.2 for late outcome CAD. The effect of parental CAD death on risk was not mediated by other shared risk factors for CAD. These findings were similar for those with either a mother or a father with CAD, if CAD onset in the offspring occurred before the age of 60 years. For persons with CAD at age 60 years or older, maternal CAD death was a stronger predictor of CAD than paternal CAD death. The association with parental history of CAD was similar among men and women in the cohort, with adjusted relative risks of 1.3 and 1.2, respectively. However, early age of parental CAD death may account for the association among women (RR = 1.6), whereas late age of CAD death for either parent was associated with the risk of CAD among men (RR = 1.4).