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Grant Details

Grant Number: 2R01CA088164-12A1 Interpret this number
Primary Investigator: Witte, John
Organization: University Of California, San Francisco
Project Title: Genetic Epidemiology of Prostate Cancer Risk and Progression
Fiscal Year: 2013


Abstract

DESCRIPTION (provided by applicant): Prostate cancer is a common but complex disease with a number of unresolved issues surrounding its natural history. These include concerns with screening, detection, and treatment, and reflect the substantial heterogeneity in prostate tumors: some will remain latent and have little impact on morbidity, whereas others progress rapidly in a potentially lethal manner. Genetic factors likely underlie some of these differences, and we propose a comprehensive evaluation of the genetic basis of prostate cancer risk and progression in a large, well-characterized study population. In particular, we will investigate rar functional variants across the exome and common SNPs across the genome. Our sample encompasses 8,078 prostate cancer cases and 8,078 age and ethnicity matched controls nested within the Kaiser / USCF Research Program on Genes, Environment and Health cohort. This population has existing genome-wide SNP measures, and uniformly collected clinical information on prostate cancer screening, diagnoses, and progression. We plan to type the new exome array on the cases and controls to assess the functional variants in protein coding regions across the human genome. With these data we will address our hypothesis that these genetic factors can be used to predict-and underlie an increasing proportion of the variation in-prostate cancer risk and progression. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these factors impact the natural history of prostate cancer. Our findings should supply important insights into the underlying mechanism of disease, with the ultimate goal of helping to improve screening and treatment for prostate cancer.



Publications

Unraveling the genetic landscape of susceptibility to multiple primary cancers.
Authors: Middha P. , Kachuri L. , Nierenberg J.L. , Graff R.E. , Cavazos T.B. , Hoffmann T.J. , Zhang J. , Alexeeff S. , Habel L. , Corley D.A. , et al. .
Source: Medrxiv : The Preprint Server For Health Sciences, 2024-10-30 00:00:00.0; , .
EPub date: 2024-10-30 00:00:00.0.
PMID: 39574869
Related Citations

Cell-free DNA concentration and fragment size as a biomarker for prostate cancer.
Authors: Chen E. , Cario C.L. , Leong L. , Lopez K. , Márquez C.P. , Chu C. , Li P.S. , Oropeza E. , Tenggara I. , Cowan J. , et al. .
Source: Scientific Reports, 2021-03-03 00:00:00.0; 11(1), p. 5040.
EPub date: 2021-03-03 00:00:00.0.
PMID: 33658587
Related Citations

Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.
Authors: Graff R.E. , Cavazos T.B. , Thai K.K. , Kachuri L. , Rashkin S.R. , Hoffman J.D. , Alexeeff S.E. , Blatchins M. , Meyers T.J. , Leong L. , et al. .
Source: Nature Communications, 2021-02-12 00:00:00.0; 12(1), p. 970.
EPub date: 2021-02-12 00:00:00.0.
PMID: 33579919
Related Citations

Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing.
Authors: Chen E. , Cario C.L. , Leong L. , Lopez K. , Márquez C.P. , Li P.S. , Oropeza E. , Tenggara I. , Cowan J. , Simko J.P. , et al. .
Source: Jco Precision Oncology, 2021; 5, .
EPub date: 2021-04-27 00:00:00.0.
PMID: 34250416
Related Citations

A large-scale association study detects novel rare variants, risk genes, functional elements, and polygenic architecture of prostate cancer susceptibility.
Authors: Emami N.C. , Cavazos T.B. , Rashkin S.R. , Graff R.E. , Tai C.G. , Mefford J.A. , Kachuri L. , Cario C.L. , Wan E. , Wong S. , et al. .
Source: Cancer Research, 2020-12-08 00:00:00.0; , .
EPub date: 2020-12-08 00:00:00.0.
PMID: 33293427
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Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
Authors: Rashkin S.R. , Graff R.E. , Kachuri L. , Thai K.K. , Alexeeff S.E. , Blatchins M.A. , Cavazos T.B. , Corley D.A. , Emami N.C. , Hoffman J.D. , et al. .
Source: Nature Communications, 2020-09-04 00:00:00.0; 11(1), p. 4423.
EPub date: 2020-09-04 00:00:00.0.
PMID: 32887889
Related Citations

A machine learning approach to optimizing cell-free DNA sequencing panels: with an application to prostate cancer.
Authors: Cario C.L. , Chen E. , Leong L. , Emami N.C. , Lopez K. , Tenggara I. , Simko J.P. , Friedlander T.W. , Li P.S. , Paris P.L. , et al. .
Source: Bmc Cancer, 2020-08-28 00:00:00.0; 20(1), p. 820.
EPub date: 2020-08-28 00:00:00.0.
PMID: 32859160
Related Citations

Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms.
Authors: Emami N.C. , Kachuri L. , Meyers T.J. , Das R. , Hoffman J.D. , Hoffmann T.J. , Hu D. , Shan J. , Feng F.Y. , Ziv E. , et al. .
Source: Nature Communications, 2019-07-15 00:00:00.0; 10(1), p. 3107.
EPub date: 2019-07-15 00:00:00.0.
PMID: 31308362
Related Citations

Orchid: a novel management, annotation and machine learning framework for analyzing cancer mutations.
Authors: Cario C.L. , Witte J.S. .
Source: Bioinformatics (oxford, England), 2018-03-15 00:00:00.0; 34(6), p. 936-942.
PMID: 29106441
Related Citations

An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations.
Authors: Majumdar A. , Haldar T. , Bhattacharya S. , Witte J.S. .
Source: Plos Genetics, 2018 02; 14(2), p. e1007139.
EPub date: 2018-02-12 00:00:00.0.
PMID: 29432419
Related Citations

Identification of Pleiotropic Cancer Susceptibility Variants from Genome-Wide Association Studies Reveals Functional Characteristics.
Authors: Wu Y.H. , Graff R.E. , Passarelli M.N. , Hoffman J.D. , Ziv E. , Hoffmann T.J. , Witte J.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2018 Jan; 27(1), p. 75-85.
EPub date: 2017-11-17 00:00:00.0.
PMID: 29150481
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Update on the State of the Science for Analytical Methods for Gene-Environment Interactions.
Authors: Gauderman W.J. , Mukherjee B. , Aschard H. , Hsu L. , Lewinger J.P. , Patel C.J. , Witte J.S. , Amos C. , Tai C.G. , Conti D. , et al. .
Source: American Journal Of Epidemiology, 2017-10-01 00:00:00.0; 186(7), p. 762-770.
PMID: 28978192
Related Citations

Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer.
Authors: Graff R.E. , Möller S. , Passarelli M.N. , Witte J.S. , Skytthe A. , Christensen K. , Tan Q. , Adami H.O. , Czene K. , Harris J.R. , et al. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2017 Aug; 15(8), p. 1256-1264.
EPub date: 2017-01-24 00:00:00.0.
PMID: 28130150
Related Citations

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.
Authors: Conti D.V. , Wang K. , Sheng X. , Bensen J.T. , Hazelett D.J. , Cook M.B. , Ingles S.A. , Kittles R.A. , Strom S.S. , Rybicki B.A. , et al. .
Source: Journal Of The National Cancer Institute, 2017-08-01 00:00:00.0; 109(8), .
PMID: 29117387
Related Citations

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.
Authors: Ng M.C.Y. , Graff M. , Lu Y. , Justice A.E. , Mudgal P. , Liu C.T. , Young K. , Yanek L.R. , Feitosa M.F. , Wojczynski M.K. , et al. .
Source: Plos Genetics, 2017 Apr; 13(4), p. e1006719.
EPub date: 2017-04-21 00:00:00.0.
PMID: 28430825
Related Citations

Tissue Sources For Accurate Measurement Of Germline Dna Genotypes In Prostate Cancer Patients Treated With Radical Prostatectomy
Authors: Emami N.C. , Leong L. , Wan E. , Van Blarigan E.L. , Cooperberg M.R. , Tenggara I. , Carroll P.R. , Chan J.M. , Witte J.S. , Simko J.P. .
Source: The Prostate, 2017 Mar; 77(4), p. 425-434.
PMID: 27900799
Related Citations

Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk.
Authors: Hoffman J.D. , Graff R.E. , Emami N.C. , Tai C.G. , Passarelli M.N. , Hu D. , Huntsman S. , Hadley D. , Leong L. , Majumdar A. , et al. .
Source: Plos Genetics, 2017 Mar; 13(3), p. e1006690.
EPub date: 2017-03-31 00:00:00.0.
PMID: 28362817
Related Citations

Genome-wide Association Study Of Prostate-specific Antigen Levels Identifies Novel Loci Independent Of Prostate Cancer
Authors: Hoffmann T.J. , Passarelli M.N. , Graff R.E. , Emami N.C. , Sakoda L.C. , Jorgenson E. , Habel L.A. , Shan J. , Ranatunga D.K. , Quesenberry C.P. , et al. .
Source: Nature Communications, 2017-01-31 00:00:00.0; 8, p. 14248.
PMID: 28139693
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A Meta-analysis Of Multiple Myeloma Risk Regions In African And European Ancestry Populations Identifies Putatively Functional Loci
Authors: Rand K.A. , Song C. , Dean E. , Serie D.J. , Curtin K. , Sheng X. , Hu D. , Huff C.A. , Bernal-Mizrachi L. , Tomasson M.H. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Dec; 25(12), p. 1609-1618.
PMID: 27587788
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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.
Authors: Han Y. , Rand K.A. , Hazelett D.J. , Ingles S.A. , Kittles R.A. , Strom S.S. , Rybicki B.A. , Nemesure B. , Isaacs W.B. , Stanford J.L. , et al. .
Source: Journal Of The National Cancer Institute, 2016 Jul; 108(7), .
PMID: 26823525
Related Citations

Selection And Explosive Growth Alter Genetic Architecture And Hamper The Detection Of Causal Rare Variants
Authors: Uricchio L.H. , Zaitlen N.A. , Ye C.J. , Witte J.S. , Hernandez R.D. .
Source: Genome Research, 2016 Jul; 26(7), p. 863-73.
PMID: 27197206
Related Citations

Determining Which Phenotypes Underlie A Pleiotropic Signal
Authors: Majumdar A. , Haldar T. , Witte J.S. .
Source: Genetic Epidemiology, 2016 Jul; 40(5), p. 366-81.
PMID: 27238845
Related Citations

Mutational Landscape Of Aggressive Prostate Tumors In African American Men
Authors: Lindquist K.J. , Paris P.L. , Hoffmann T.J. , Cardin N.J. , Kazma R. , Mefford J.A. , Simko J.P. , Ngo V. , Chen Y. , Levin A.M. , et al. .
Source: Cancer Research, 2016-04-01 00:00:00.0; 76(7), p. 1860-8.
PMID: 26921337
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Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.
Authors: Rand K.A. , Rohland N. , Tandon A. , Stram A. , Sheng X. , Do R. , Pasaniuc B. , Allen A. , Quinque D. , Mallick S. , et al. .
Source: Human Molecular Genetics, 2016-01-15 00:00:00.0; 25(2), p. 371-81.
EPub date: 2016-01-15 00:00:00.0.
PMID: 26604137
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A Cross-cancer Genetic Association Analysis Of The Dna Repair And Dna Damage Signaling Pathways For Lung, Ovary, Prostate, Breast, And Colorectal Cancer
Authors: Scarbrough P.M. , Weber R.P. , Iversen E.S. , Brhane Y. , Amos C.I. , Kraft P. , Hung R.J. , Sellers T.A. , Witte J.S. , Pharoah P. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jan; 25(1), p. 193-200.
PMID: 26637267
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Semiparametric Allelic Tests For Mapping Multiple Phenotypes: Binomial Regression And Mahalanobis Distance
Authors: Majumdar A. , Witte J.S. , Ghosh S. .
Source: Genetic Epidemiology, 2015 Dec; 39(8), p. 635-50.
PMID: 26493781
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Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.
Authors: Han Y. , Hazelett D.J. , Wiklund F. , Schumacher F.R. , Stram D.O. , Berndt S.I. , Wang Z. , Rand K.A. , Hoover R.N. , Machiela M.J. , et al. .
Source: Human Molecular Genetics, 2015-10-01 00:00:00.0; 24(19), p. 5603-18.
EPub date: 2015-10-01 00:00:00.0.
PMID: 26162851
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Strategies For Imputing And Analyzing Rare Variants In Association Studies
Authors: Hoffmann T.J. , Witte J.S. .
Source: Trends In Genetics : Tig, 2015 Oct; 31(10), p. 556-63.
PMID: 26450338
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Detecting Gene-environment Interactions In Human Birth Defects: Study Designs And Statistical Methods
Authors: Tai C.G. , Graff R.E. , Liu J. , Passarelli M.N. , Mefford J.A. , Shaw G.M. , Hoffmann T.J. , Witte J.S. .
Source: Birth Defects Research. Part A, Clinical And Molecular Teratology, 2015 Aug; 103(8), p. 692-702.
PMID: 26010994
Related Citations

A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences.
Authors: Hoffmann T.J. , Van Den Eeden S.K. , Sakoda L.C. , Jorgenson E. , Habel L.A. , Graff R.E. , Passarelli M.N. , Cario C.L. , Emami N.C. , Chao C.R. , et al. .
Source: Cancer Discovery, 2015 Aug; 5(8), p. 878-91.
PMID: 26034056
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Replication And Heritability Of Prostate Cancer Risk Variants: Impact Of Population-specific Factors
Authors: Virlogeux V. , Graff R.E. , Hoffmann T.J. , Witte J.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Jun; 24(6), p. 938-43.
PMID: 25809866
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Generalizability of established prostate cancer risk variants in men of African ancestry.
Authors: Han Y. , Signorello L.B. , Strom S.S. , Kittles R.A. , Rybicki B.A. , Stanford J.L. , Goodman P.J. , Berndt S.I. , Carpten J. , Casey G. , et al. .
Source: International Journal Of Cancer, 2015-03-01 00:00:00.0; 136(5), p. 1210-7.
EPub date: 2015-03-01 00:00:00.0.
PMID: 25044450
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Selenoprotein and antioxidant genes and the risk of high-grade prostate cancer and prostate cancer recurrence.
Authors: Gerstenberger J.P. , Bauer S.R. , Van Blarigan E.L. , Sosa E. , Song X. , Witte J.S. , Carroll P.R. , Chan J.M. .
Source: The Prostate, 2015 Jan; 75(1), p. 60-9.
PMID: 25284284
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Population Genetic Simulations Of Complex Phenotypes With Implications For Rare Variant Association Tests
Authors: Uricchio L.H. , Torres R. , Witte J.S. , Hernandez R.D. .
Source: Genetic Epidemiology, 2015 Jan; 39(1), p. 35-44.
PMID: 25417809
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Imputation Of The Rare Hoxb13 G84e Mutation And Cancer Risk In A Large Population-based Cohort
Authors: Hoffmann T.J. , Sakoda L.C. , Shen L. , Jorgenson E. , Habel L.A. , Liu J. , Kvale M.N. , Asgari M.M. , Banda Y. , Corley D. , et al. .
Source: Plos Genetics, 2015 Jan; 11(1), p. e1004930.
PMID: 25629170
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The contribution of genetic variants to disease depends on the ruler.
Authors: Witte J.S. , Visscher P.M. , Wray N.R. .
Source: Nature Reviews. Genetics, 2014 11; 15(11), p. 765-76.
PMID: 25223781
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Authors: Al Olama A.A. , Kote-Jarai Z. , Berndt S.I. , Conti D.V. , Schumacher F. , Han Y. , Benlloch S. , Hazelett D.J. , Wang Z. , Saunders E. , et al. .
Source: Nature Genetics, 2014 Oct; 46(10), p. 1103-9.
PMID: 25217961
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Performance Of The Genomic Evaluators Of Metastatic Prostate Cancer (gemcap) Tumor Biomarker For Identifying Recurrent Disease In African American Patients
Authors: Levin A.M. , Lindquist K.J. , Avila A. , Witte J.S. , Paris P.L. , Rybicki B.A. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Aug; 23(8), p. 1677-82.
PMID: 24891551
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Antioxidant and vitamin E transport genes and risk of high-grade prostate cancer and prostate cancer recurrence.
Authors: Bauer S.R. , Richman E.L. , Sosa E. , Weinberg V. , Song X. , Witte J.S. , Carroll P.R. , Chan J.M. .
Source: The Prostate, 2013 Dec; 73(16), p. 1786-95.
PMID: 24038157
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda K.L. , Chen G.K. , Taylor K.C. , Palmer C. , Edwards T.L. , Lange L.A. , Ng M.C. , Adeyemo A.A. , Allison M.A. , Bielak L.F. , et al. .
Source: Nature Genetics, 2013 Jun; 45(6), p. 690-6.
PMID: 23583978
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The Impact Of Improved Microarray Coverage And Larger Sample Sizes On Future Genome-wide Association Studies
Authors: Lindquist K.J. , Jorgenson E. , Hoffmann T.J. , Witte J.S. .
Source: Genetic Epidemiology, 2013 May; 37(4), p. 383-92.
PMID: 23529720
Related Citations

Hoxb13 Mutation And Prostate Cancer: Studies Of Siblings And Aggressive Disease
Authors: Witte J.S. , Mefford J. , Plummer S.J. , Liu J. , Cheng I. , Klein E.A. , Rybicki B.A. , Casey G. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 Apr; 22(4), p. 675-80.
PMID: 23396964
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Turning Of Cogs Moves Forward Findings For Hormonally Mediated Cancers
Authors: Sakoda L.C. , Jorgenson E. , Witte J.S. .
Source: Nature Genetics, 2013 Apr; 45(4), p. 345-8.
PMID: 23535722
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Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent.
Authors: Rebbeck T.R. , Devesa S.S. , Chang B.L. , Bunker C.H. , Cheng I. , Cooney K. , Eeles R. , Fernandez P. , Giri V.N. , Gueye S.M. , et al. .
Source: Prostate Cancer, 2013; 2013, p. 560857.
PMID: 23476788
Related Citations

Rare genetic variants and treatment response: sample size and analysis issues.
Authors: Witte J.S. .
Source: Statistics In Medicine, 2012-11-10 00:00:00.0; 31(25), p. 3041-50.
EPub date: 2012-11-10 00:00:00.0.
PMID: 22736504
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Joint association testing of common and rare genetic variants using hierarchical modeling.
Authors: Cardin N.J. , Mefford J.A. , Witte J.S. .
Source: Genetic Epidemiology, 2012 Sep; 36(6), p. 642-51.
PMID: 22807252
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Copy number alterations in prostate tumors and disease aggressiveness.
Authors: Cheng I. , Levin A.M. , Tai Y.C. , Plummer S. , Chen G.K. , Neslund-Dudas C. , Casey G. , Rybicki B.A. , Witte J.S. .
Source: Genes, Chromosomes & Cancer, 2012 Jan; 51(1), p. 66-76.
PMID: 21965145
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The Covariate's Dilemma.
Authors: Mefford J. , Witte J.S. .
Source: Plos Genetics, 2012; 8(11), p. e1003096.
PMID: 23162385
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Association Of The Innate Immunity And Inflammation Pathway With Advanced Prostate Cancer Risk
Authors: Kazma R. , Mefford J.A. , Cheng I. , Plummer S.J. , Levin A.M. , Rybicki B.A. , Casey G. , Witte J.S. .
Source: Plos One, 2012; 7(12), p. e51680.
PMID: 23272139
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Does Accounting For Gene-environment Interactions Help Uncover Association Between Rare Variants And Complex Diseases?
Authors: Kazma R. , Cardin N.J. , Witte J.S. .
Source: Human Heredity, 2012; 74(3-4), p. 205-14.
PMID: 23594498
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