@article {950, title = {8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 03 23}, pages = {1523}, abstract = {

The 8q24 genomic locus is tied to the origin of numerous cancers. We investigate its contribution to hereditary prostate cancer (HPC) in independent study populations of the Nashville Familial Prostate Cancer Study and International Consortium for Prostate Cancer Genetics (combined: 2,836 HPC cases, 2,206 controls of European ancestry). Here we report 433 variants concordantly associated with HPC in both study populations, accounting for 9\% of heritability and modifying age of diagnosis as well as aggressiveness; 183 reach genome-wide significance. The variants comprehensively distinguish independent risk-altering haplotypes overlapping the 648 kb locus (three protective, and four risk (peak odds ratios: 1.5, 4, 5, and 22)). Sequence of the near-Mendelian haplotype reveals eleven causal mutation candidates. We introduce a linkage disequilibrium-based algorithm discerning eight independent sentinel variants, carrying considerable risk prediction ability (AUC = 0.625) for a single locus. These findings elucidate 8q24 locus structure and correlates for clinical prediction of prostate cancer risk.

}, keywords = {Aged, Case-Control Studies, Chromosomes, Human, Pair 8, European Continental Ancestry Group, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Heterozygote, Humans, Linkage Disequilibrium, Male, Middle Aged, Mutation, Prostatic Neoplasms, Protective Factors, Risk Factors}, issn = {2041-1723}, doi = {10.1038/s41467-020-15122-1}, author = {Dupont, William D and Breyer, Joan P and Plummer, W Dale and Chang, Sam S and Cookson, Michael S and Smith, Joseph A and Blue, Elizabeth E and Bamshad, Michael J and Smith, Jeffrey R} } @article {303, title = {Attitudes of African Americans toward return of results from exome and whole genome sequencing.}, journal = {Am J Med Genet A}, volume = {161A}, year = {2013}, month = {2013 May}, pages = {1064-72}, abstract = {

Exome sequencing and whole genome sequencing (ES/WGS) present patients and research participants with the opportunity to benefit from a broad scope of genetic results of clinical and personal utility. Yet, this potential for benefit also risks disenfranchising populations such as African Americans (AAs) that are already underrepresented in genetic research and utilize genetic tests at lower rates than other populations. Understanding a diverse range of perspectives on consenting for ES/WGS and receiving ES/WGS results is necessary to ensure parity in genomic health care and research. We conducted a series of 13 focus groups (n = 76) to investigate if and how attitudes toward participation in ES/WGS research and return of results from ES/WGS differ between self-described AAs and non-AAs. The majority of both AAs and non-AAs were willing to participate in WGS studies and receive individual genetic results, but the fraction not interested in either was higher in AAs. This is due in part to different expectations of health benefits from ES/WGS and how results should be managed. Our results underscore the need to develop and test culturally tailored strategies for returning ES/WGS results to AAs.

}, keywords = {Adult, African Americans, Aged, Attitude, Exome, Female, Focus Groups, Genetic Research, Genome-Wide Association Study, Humans, Male, Middle Aged, Sequence Analysis, DNA, Surveys and Questionnaires, Washington}, issn = {1552-4833}, doi = {10.1002/ajmg.a.35914}, author = {Yu, Joon-Ho and Crouch, Julia and Jamal, Seema M and Tabor, Holly K and Bamshad, Michael J} } @article {325, title = {The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions.}, journal = {Am J Med Genet A}, volume = {158A}, year = {2012}, month = {2012 Jul}, pages = {1523-5}, abstract = {

Next generation exome sequencing (ES) and whole genome sequencing (WGS) are new powerful tools for discovering the gene(s) that underlie Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Genomics at Yale University; and the Baylor-Johns Hopkins Center for Mendelian Genomics at Baylor College of Medicine and Johns Hopkins University. The CMGs will provide ES/WGS and extensive analysis expertise at no cost to collaborating investigators where the causal gene(s) for a Mendelian phenotype has yet to be uncovered. Over the next few years and in collaboration with the global human genetics community, the CMGs hope to facilitate the identification of the genes underlying a very large fraction of all Mendelian disorders; see http://mendelian.org.

}, keywords = {Academies and Institutes, Genetic Diseases, Inborn, Genetics, Medical, Genome, Human, Genome-Wide Association Study, Genomics, High-Throughput Nucleotide Sequencing, Humans}, issn = {1552-4833}, doi = {10.1002/ajmg.a.35470}, author = {Bamshad, Michael J and Shendure, Jay A and Valle, David and Hamosh, Ada and Lupski, James R and Gibbs, Richard A and Boerwinkle, Eric and Lifton, Richard P and Gerstein, Mark and G{\"u}nel, Murat and Mane, Shrikant and Nickerson, Deborah A} }