Browsing by Author "Freedman, Matthew L."
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Item Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men(2006) Freedman, Matthew L.; Haiman, Christopher A.; Patterson, Nick; McDonald, Gavin J.; Tandon, Arti; Waliszewska, Alicja; Penney, Kathryn; Steen, Robert G.; Kristin Ardlie, Kristin; John, Esther M.; Oakley-Girvan, Ingrid; Whittemore, Alice S.; Cooney, Kathleen A.; Ingles, Sue A.; Altshuler, David; Henderson, Brian E.; Reich, DavidA whole-genome admixture scan in 1,597 African Americans identified a 3.8Mbinterval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD)7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P<4.2109) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.Item Location Choice, Product Choice, and the Human Resource Practices of Firms(2007-05-10) Freedman, Matthew L.; Haltiwanger, John C; Economics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis is comprised of three chapters. The first investigates the implications of industrial clustering for labor mobility and earnings dynamics. Motivated by a theoretical model in which geographically clustered firms compete for workers, I exploit establishment-level variation in agglomeration to explore the impact of clustering in the software publishing industry on labor market outcomes. The results show that clustering makes it easier for workers to job hop among establishments within the sector. Further, workers in clusters have relatively steep earnings-tenure profiles, accepting lower wages early in their careers in exchange for stronger earnings growth and higher wages later. These findings underscore the importance of geography in understanding labor market dynamics within industries. While the first chapter reveals striking relationships between the human resource practices and location decisions of high-technology establishments, the second chapter (joint with F. Andersson, J. Haltiwanger, J. Lane, and K. Shaw) draws key connections between the hiring and compensation policies of innovative firms and the nature of their product markets. We show that software firms that operate in product markets with highly skewed returns to innovation pay a premium to attract talented workers. Yet these same firms also reward loyalty; that is, highly skilled workers faithful to their employers enjoy higher earnings in firms with a greater variance in potential payoffs from innovation. These results not only contribute to our knowledge of firm human resource practices and product market strategies, but also shed light on patterns of income inequality within and between industries. Building on this final idea, the last chapter (joint with F. Andersson, E. Davis, J. Lane, B. McCall, and L. Sandusky) examines the contribution of worker and firm reallocation to within-industry changes in earnings inequality. We find that the entry and exit of firms and the sorting of workers and firms based on worker skills are key determinants of changes in industry earnings distributions over time. However, the importance of these and other factors in driving observed dynamics in earnings inequality varies across sectors, with aggregate shifts often disguising fundamental differences in the underlying forces effecting change.Item Systematic Evaluation of Genetic Variation at the Androgen Receptor Locus and Risk of Prostate Cancer in a Multiethnic Cohort Study(2005) Freedman, Matthew L.; Pearce, Celeste L.; Penney, Kathryn L.; Hirschhorn, Joel N.; Kolonel, Laurence N.; Henderson, Brian E.; Altshuler, DavidRepeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of >20 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in >4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease.