Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes

BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six associations yielded p <10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p = 4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies.

Systematic Review of Supported Housing Literature 1993 – 2008

Supported housing for individuals with severe mental illness strives to provide the services necessary to place and keep individuals in independent housing that is integrated into the community and in which the consumer has choice and control over his or her services and supports. Supported housing can be contrasted to an earlier model called the “linear residential approach” in which individuals are moved from the most restrictive settings (e.g., inpatient settings) through a series of more independent settings (e.g., group homes, supervised apartments) and then finally to independent housing. This approach has been criticized as punishing the client due to frequent moves, and as being less likely to result in independent housing. In the supported housing model (Anthony & Blanch, 1988) consumers have choice and control over their living environment, their treatment, and supports (e.g., case management, mental health and substance abuse services). Supports are flexible and faded in and out depending on needs. Results of this systematic review of supported housing suggest that there are several well-controlled studies of supported housing and several studies conducted with less rigorous designs. Overall, our synthesis suggests that supported housing can improve the living situation of individuals who are psychiatrically disabled, homeless and with substance abuse problems. Results show that supported housing can help people stay in apartments or homes up to about 80% of the time over an extended period. These results are contrary to concerns expressed by proponents of the linear residential model and housing models that espoused more restrictive environments. Results also show that housing subsidies or vouchers are helpful in getting and keeping individuals housed. Housing services appear to be cost effective and to reduce the costs of other social and clinical services. In order to be most effective, intensive case management services (rather than traditional case management) are needed and will generally lead to better housing outcomes. Having access to affordable housing and having a service system that is well-integrated is also important. Providing a person with supported housing reduces the likelihood that they will be re-hospitalized, although supported housing does not always lead to reduced psychiatric symptoms. Supported housing can improve clients’ quality of life and satisfaction with their living situation. Providing supported housing options that are of decent quality is important in order to keep people housed and satisfied with their housing. In addition, rapid entry into housing, with the provision of choices is critical. Program and clinical supports may be able to mitigate the social isolation that has sometimes been associated with supported housing.