Objective: The proposed research seeks to evaluate the comparative effectiveness of genomic health risk assessments for common chronic health conditions. Genomic risk scores (GRS) will be developed for three different types of health conditions: the extreme of a physical trait that is normally distributed in the population (obesity), a medical diagnosis (asthma), and a psychiatric diagnosis (alcohol dependence). GRS will then be compared to an established risk assessment which indexes the prevalence of the health condition among an individual's relatives, a family history score. Analyses will test whether genomic information is comparably effective to family history information in identifying at risk individuals and whether combining the two sources information improves risk assessment. Methods: GRS will be developed for obesity, asthma, and alcohol dependence from sets of risk variants called single nucleotide polymorph/isms (SNPs) that have been identified in massive case-control studies called genome-wide association studies (GWAS). GRS will be validated using data from the Dunedin Longitudinal Study, a birth cohort study of 1,037 individuals followed through age 38 years, and from three large GWAS datasets obtained from the National Institutes of Health. Validated GRS will be compared to family history-based risk assessments using data from the Dunedin Study. Analyses will consider three outcomes: (1) early onset in childhood, (2) chronic persistence from young adulthood through mid-life, and (3) adult severity. For each outcome, the proposed study will compare the sensitivity and specificity of GRS-based risk assessment to risk assessment using the family history score (clinical validity) and test whether combining information from the GRS and the family history score improves the identification of at risk individuals (clinical utility). Further analyses will examine whether clinical validity and utility vary depending on baseline levels of risk defined by family history and early life risk exposures. Contributions and Significance: The proposed research will inform the translation of genome science into public health practice by testing a new method of risk assessment for obesity, asthma, and alcohol dependence, and will provide a sound evidence base for the evaluation and regulation of direct-to consumer genomic testing services.
The proposed research is relevant to public health in two ways: First, it will test a new method of health risk assessment that can be used to identify at risk individuals before symptoms develop. Second, it will inform the development of policies to regulate direct-to-consumer and clinic-based uses of genomic information in health risk assessment. Tests of the comparative effectiveness of using genomic information in health risk assessments will aid in the translation of genome science to public health practice and the development of policy to regulate the use of genomic information.
|Belsky, Daniel W; Sears, Malcolm R; Hancox, Robert J et al. (2013) Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study. Lancet Respir Med 1:453-61|
|Belsky, Daniel W; Moffitt, Terrie E; Sugden, Karen et al. (2013) Development and evaluation of a genetic risk score for obesity. Biodemography Soc Biol 59:85-100|
|Belsky, Daniel W; Moffitt, Terrie E; Baker, Timothy B et al. (2013) Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: evidence from a 4-decade longitudinal study. JAMA Psychiatry 70:534-42|
|Belsky, Daniel W; Moffitt, Terrie E; Caspi, Avshalom (2013) Genetics in population health science: strategies and opportunities. Am J Public Health 103 Suppl 1:S73-83|
|Belsky, Daniel W; Moffitt, Terrie E; Houts, Renate et al. (2012) Polygenic risk, rapid childhood growth, and the development of obesity: evidence from a 4-decade longitudinal study. Arch Pediatr Adolesc Med 166:515-21|