Browsing by Author "Nelson, Sarah C"

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    A content analysis of the views of genetics professionals on race, ancestry, and genetics.
    (AJOB empirical bioethics, 2018-10) Nelson, Sarah C; Yu, Joon-Ho; Wagner, Jennifer K; Harrell, Tanya M; Royal, Charmaine D; Bamshad, Michael J
    Over the past decade, the proliferation of genetic studies on human health and disease has reinvigorated debates about the appropriate role of race and ancestry in research and clinical care. Here we report on the responses of genetics professionals to a survey about their views on race, genetics, and ancestry across the domains of science, medicine, and society. Through a qualitative content analysis of free-text comments from 515 survey respondents, we identified key themes pertaining to multiple meanings of race, the use of race as a proxy for genetic ancestry, and the relevance of race and ancestry to health. Our findings suggest that for many genetics professionals the questions of what race is and what race means remain both professionally and personally contentious. Looking ahead as genomics is translated into the practice of precision medicine and as learning health care systems offer continued improvements in care through integrated research, we argue for nuanced considerations of both race and genetic ancestry across research and care settings.
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    Detectable clonal mosaicism from birth to old age and its relationship to cancer.
    (Nature genetics, 2012-05-06) Laurie, Cathy C; Laurie, Cecelia A; Rice, Kenneth; Doheny, Kimberly F; Zelnick, Leila R; McHugh, Caitlin P; Ling, Hua; Hetrick, Kurt N; Pugh, Elizabeth W; Amos, Chris; Wei, Qingyi; Wang, Li-e; Lee, Jeffrey E; Barnes, Kathleen C; Hansel, Nadia N; Mathias, Rasika; Daley, Denise; Beaty, Terri H; Scott, Alan F; Ruczinski, Ingo; Scharpf, Rob B; Bierut, Laura J; Hartz, Sarah M; Landi, Maria Teresa; Freedman, Neal D; Goldin, Lynn R; Ginsburg, David; Li, Jun; Desch, Karl C; Strom, Sara S; Blot, William J; Signorello, Lisa B; Ingles, Sue A; Chanock, Stephen J; Berndt, Sonja I; Le Marchand, Loic; Henderson, Brian E; Monroe, Kristine R; Heit, John A; de Andrade, Mariza; Armasu, Sebastian M; Regnier, Cynthia; Lowe, William L; Hayes, M Geoffrey; Marazita, Mary L; Feingold, Eleanor; Murray, Jeffrey C; Melbye, Mads; Feenstra, Bjarke; Kang, Jae H; Wiggs, Janey L; Jarvik, Gail P; McDavid, Andrew N; Seshan, Venkatraman E; Mirel, Daniel B; Crenshaw, Andrew; Sharopova, Nataliya; Wise, Anastasia; Shen, Jess; Crosslin, David R; Levine, David M; Zheng, Xiuwen; Udren, Jenna I; Bennett, Siiri; Nelson, Sarah C; Gogarten, Stephanie M; Conomos, Matthew P; Heagerty, Patrick; Manolio, Teri; Pasquale, Louis R; Haiman, Christopher A; Caporaso, Neil; Weir, Bruce S
    We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).
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    Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.
    (Pain, 2018-11-13) Smith, Shad B; Parisien, Marc; Bair, Eric; Belfer, Inna; Chabot-Doré, Anne-Julie; Gris, Pavel; Khoury, Samar; Tansley, Shannon; Torosyan, Yelizaveta; Zaykin, Dmitri V; Bernhardt, Olaf; de Oliveira Serrano, Priscila; Gracely, Richard H; Jain, Deepti; Järvelin, Marjo-Riitta; Kaste, Linda M; Kerr, Kathleen F; Kocher, Thomas; Lähdesmäki, Raija; Laniado, Nadia; Laurie, Cathy C; Laurie, Cecelia A; Männikkö, Minna; Meloto, Carolina B; Nackley, Andrea G; Nelson, Sarah C; Pesonen, Paula; Ribeiro-Dasilva, Margarete C; Rizzatti-Barbosa, Celia M; Sanders, Anne E; Schwahn, Christian; Sipilä, Kirsi; Sofer, Tamar; Teumer, Alexander; Mogil, Jeffrey S; Fillingim, Roger B; Greenspan, Joel D; Ohrbach, Richard; Slade, Gary D; Maixner, William; Diatchenko, Luda
    Painful temporomandibular disorders (TMD) is the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. While many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a GWAS assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified three distinct loci that were significant in combined or sex-segregated analyses. A single nucleotide polymorphism (SNP) on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio [OR]=2.9, 95% CI: 2.02-4.27, P=2.2x10). This association was nominally replicated in a meta-analysis of seven independent orofacial pain cohorts including 160,194 participants (OR=1.16, 95% CI: 1.0-1.35, P = 2.3x10). Functional analysis in human dorsal root ganglia (DRG) and blood indicated this variant is an expression quantitative trait locus (eQTL), with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43x10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically-determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.