Grant Details
Grant Number: |
5U01CA136792-03 Interpret this number |
Primary Investigator: |
Henderson, Brian |
Organization: |
University Of Southern California |
Project Title: |
A Genome-Wide Association Study of Prostate Cancer in African Americans |
Fiscal Year: |
2011 |
Abstract
DESCRIPTION (provided by applicant): Prostate cancer is one of the leading causes of morbidity and mortality among men. We do not have an understanding of the underlying etiology of prostate cancer, or why different groups such as African Americans have higher rates of this disease. Risk factors for prostate cancer have remained elusive, other than age, having a family history of the disease and African ancestry, until recently with the discovery of multiple disease risk loci utilizing Genome Wide Association Studies( GWAS ). The first such loci were discovered in a gene " desert " in 8q24, and now the total number of loci number at least 30. Many of the allelic loci identified since those in 8q24, lie within introns or nearby known gene regions. Given the SNP density of the current tools used for GWAS, virtually all the risk loci identified have been found to be common allelic variants and the relative risk of prostate cancer from each such risk locus tends to be modest, e.g. 1.1-1.3. While differences in the frequency of such individual risk alleles, particularly in the 8q24 region, can partially account for the higher risk in populations of African ancestry, all the risk loci detected to date account for no more than 20-25% of the familial risk of prostate cancer. It has been hypothesized that less common or rare functional risk alleles might be identifiable in those loci located within or near to known functional candidate gene regions, and that such less common or rare alleles might explain both the " signal " identified by a more common allele in LD and a somewhat greater familial and/ or population attributable risk. In this application we have assembled a multi- institutional team of investigators with experience in prostate cancer research in minority populations who are willing to pool resources for a large scale attempt to identify such less common or rare alleles. We propose to collaborate with David Reich at Harvard who has the capability to bar code and pool large numbers of DNA samples for deep sequencing across the risk regions where the common allelic variants have been discovered. To optimize our ability to identify these less common and rare variants we propose to include 4500 prostate cases and controls from the Multiethnic Cohort ( Japanese, African American, European American, Latino and Native Hawaiian ) as well as 500 African American prostate cancer cases with a family history of prostate cancer from among those populations currently participating in the collaborative GWAS of African Americans being conducted at USC. We expect this effort to significantly advance knowledge of the genetic risk factors for sporadic and familial prostate cancer among a variety of different racial/ethnic groups, including the highest risk population of African ancestry. The specific identification of the functional genetic variants in the risk loci that have been discovered by GWAS should guide the development of future preventive, early detection, prognostic and even therapeutic measures.
PUBLIC HEALTH RELEVANCE: The goal of this project is to identify less common and rare risk alleles for prostate cancer in the approximately 30 allelic loci that have been discovered by genome wide association studies. For this effort, we will utilize the resources of the Multiethnic Cohort Study populations (African American, Japanese, Latino, European American, and Native Hawaiian) as well as several of the key populations of African Americans who are part of the funded African American prostate cancer genome wide association study. More specifically we propose to sequence 4500 individuals with prostate cancer and 4500 controls from the Multiethnic Cohort Study and an additional 500 African American prostate cancer cases with a family history of prostate cancer.
Publications
Tree-based QTL mapping with expected local genetic relatedness matrices.
Authors: Link V.
, Schraiber J.G.
, Fan C.
, Dinh B.
, Mancuso N.
, Chiang C.W.K.
, Edge M.D.
.
Source: American Journal Of Human Genetics, 2023-12-07 00:00:00.0; 110(12), p. 2077-2091.
PMID: 38065072
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Assessing efficiency of fine-mapping obesity-associated variants through leveraging ancestry architecture and functional annotation using PAGE and UKBB cohorts.
Authors: Anwar M.Y.
, Graff M.
, Highland H.M.
, Smit R.
, Wang Z.
, Buchanan V.L.
, Young K.L.
, Kenny E.E.
, Fernandez-Rhodes L.
, Liu S.
, et al.
.
Source: Human Genetics, 2023 Oct; 142(10), p. 1477-1489.
EPub date: 2023-09-01 00:00:00.0.
PMID: 37658231
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The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.
Authors: Huerta-Chagoya A.
, Schroeder P.
, Mandla R.
, Deutsch A.J.
, Zhu W.
, Petty L.
, Yi X.
, Cole J.B.
, Udler M.S.
, Dornbos P.
, et al.
.
Source: Diabetologia, 2023 Jul; 66(7), p. 1273-1288.
EPub date: 2023-05-06 00:00:00.0.
PMID: 37148359
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Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations.
Authors: Anwar M.Y.
, Baldassari A.R.
, Polikowsky H.G.
, Sitlani C.M.
, Highland H.M.
, Chami N.
, Chen H.H.
, Graff M.
, Howard A.G.
, Jung S.Y.
, et al.
.
Source: Bmc Medical Genomics, 2022-09-10 00:00:00.0; 15(1), p. 192.
EPub date: 2022-09-10 00:00:00.0.
PMID: 36088317
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Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study.
Authors: Downie C.G.
, Dimos S.F.
, Bien S.A.
, Hu Y.
, Darst B.F.
, Polfus L.M.
, Wang Y.
, Wojcik G.L.
, Tao R.
, Raffield L.M.
, et al.
.
Source: Diabetologia, 2021-12-24 00:00:00.0; , .
EPub date: 2021-12-24 00:00:00.0.
PMID: 34951656
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Precise diagnosis of three top cancers using dbGaP data.
Authors: Liu X.Q.
, Liu X.S.
, Rong J.Y.
, Gao F.
, Wu Y.D.
, Deng C.H.
, Jiang H.Y.
, Li X.F.
, Chen Y.Q.
, Zhao Z.G.
, et al.
.
Source: Scientific Reports, 2021-01-12 00:00:00.0; 11(1), p. 823.
EPub date: 2021-01-12 00:00:00.0.
PMID: 33436913
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Mapping and characterization of structural variation in 17,795 human genomes.
Authors: Abel H.J.
, Larson D.E.
, Regier A.A.
, Chiang C.
, Das I.
, Kanchi K.L.
, Layer R.M.
, Neale B.M.
, Salerno W.J.
, Reeves C.
, et al.
.
Source: Nature, 2020 07; 583(7814), p. 83-89.
EPub date: 2020-05-27 00:00:00.0.
PMID: 32460305
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Multi-ethnic transcriptome-wide association study of prostate cancer.
Authors: Fiorica P.N.
, Schubert R.
, Morris J.D.
, Abdul Sami M.
, Wheeler H.E.
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Source: Plos One, 2020; 15(9), p. e0236209.
EPub date: 2020-09-28 00:00:00.0.
PMID: 32986714
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Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study.
Authors: Lin B.M.
, Nadkarni G.N.
, Tao R.
, Graff M.
, Fornage M.
, Buyske S.
, Matise T.C.
, Highland H.M.
, Wilkens L.R.
, Carlson C.S.
, et al.
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Source: Frontiers In Genetics, 2019; 10, p. 494.
EPub date: 2019-05-24 00:00:00.0.
PMID: 31178898
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A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans.
Authors: Pendergrass S.A.
, Buyske S.
, Jeff J.M.
, Frase A.
, Dudek S.
, Bradford Y.
, Ambite J.L.
, Avery C.L.
, Buzkova P.
, Deelman E.
, et al.
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Source: Plos One, 2019; 14(12), p. e0226771.
EPub date: 2019-12-31 00:00:00.0.
PMID: 31891604
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DNArCdb: A database of cancer biomarkers in DNA repair genes that includes variants related to multiple cancer phenotypes.
Authors: Silvestrov P.
, Maier S.J.
, Fang M.
, Cisneros G.A.
.
Source: Dna Repair, 2018 Oct; 70, p. 10-17.
EPub date: 2018-07-31 00:00:00.0.
PMID: 30098577
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Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.
Authors: Kocarnik J.M.
, Richard M.
, Graff M.
, Haessler J.
, Bien S.
, Carlson C.
, Carty C.L.
, Reiner A.P.
, Avery C.L.
, Ballantyne C.M.
, et al.
.
Source: Human Molecular Genetics, 2018-08-15 00:00:00.0; 27(16), p. 2940-2953.
PMID: 29878111
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The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis.
Authors: Fernández-Rhodes L.
, Malinowski J.R.
, Wang Y.
, Tao R.
, Pankratz N.
, Jeff J.M.
, Yoneyama S.
, Carty C.L.
, Setiawan V.W.
, Le Marchand L.
, et al.
.
Source: Plos One, 2018; 13(7), p. e0200486.
EPub date: 2018-07-25 00:00:00.0.
PMID: 30044860
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Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.
Authors: Gong J.
, Nishimura K.K.
, Fernandez-Rhodes L.
, Haessler J.
, Bien S.
, Graff M.
, Lim U.
, Lu Y.
, Gross M.
, Fornage M.
, et al.
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Source: International Journal Of Obesity (2005), 2017-12-21 00:00:00.0; , .
EPub date: 2017-12-21 00:00:00.0.
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Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium.
Authors: Bien S.A.
, Pankow J.S.
, Haessler J.
, Lu Y.N.
, Pankratz N.
, Rohde R.R.
, Tamuno A.
, Carlson C.S.
, Schumacher F.R.
, Bůžková P.
, et al.
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Source: Diabetologia, 2017 Dec; 60(12), p. 2384-2398.
EPub date: 2017-09-13 00:00:00.0.
PMID: 28905132
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Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.
Authors: Wang H.
, Schmit S.L.
, Haiman C.A.
, Keku T.O.
, Kato I.
, Palmer J.R.
, van den Berg D.
, Wilkens L.R.
, Burnett T.
, Conti D.V.
, et al.
.
Source: International Journal Of Cancer, 2017-06-15 00:00:00.0; 140(12), p. 2728-2733.
EPub date: 2017-06-15 00:00:00.0.
PMID: 28295283
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Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci.
Authors: Fernández-Rhodes L.
, Gong J.
, Haessler J.
, Franceschini N.
, Graff M.
, Nishimura K.K.
, Wang Y.
, Highland H.M.
, Yoneyama S.
, Bush W.S.
, et al.
.
Source: Human Genetics, 2017 Jun; 136(6), p. 771-800.
EPub date: 2017-04-08 00:00:00.0.
PMID: 28391526
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.
Authors: Justice A.E.
, Winkler T.W.
, Feitosa M.F.
, Graff M.
, Fisher V.A.
, Young K.
, Barata L.
, Deng X.
, Czajkowski J.
, Hadley D.
, et al.
.
Source: Nature Communications, 2017-04-26 00:00:00.0; 8, p. 14977.
EPub date: 2017-04-26 00:00:00.0.
PMID: 28443625
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ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding.
Authors: Walker A.R.
, Silvestrov P.
, Müller T.A.
, Podolsky R.H.
, Dyson G.
, Hausinger R.P.
, Cisneros G.A.
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Source: Plos Computational Biology, 2017 02; 13(2), p. e1005345.
EPub date: 2017-02-23 00:00:00.0.
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Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.
Authors: Mozaffarian D.
, Dashti H.S.
, Wojczynski M.K.
, Chu A.Y.
, Nettleton J.A.
, Männistö S.
, Kristiansson K.
, Reedik M.
, Lahti J.
, Houston D.K.
, et al.
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Source: Plos One, 2017; 12(12), p. e0186456.
EPub date: 2017-12-13 00:00:00.0.
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Generalization And Fine Mapping Of European Ancestry-based Central Adiposity Variants In African Ancestry Populations
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, Yao J.
, Guo X.
, Fernandez-Rhodes L.
, Lim U.
, Boston J.
, Buzková P.
, Carlson C.S.
, Cheng I.
, Cochran B.
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Source: International Journal Of Obesity (2005), 2016-11-21 00:00:00.0; , .
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KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex.
Authors: Johnson E.O.
, Hancock D.B.
, Levy J.L.
, Gaddis N.C.
, Page G.P.
, Glasheen C.
, Saccone N.L.
, Bierut L.J.
, Kral A.H.
.
Source: Addiction Biology, 2016 11; 21(6), p. 1217-1232.
PMID: 26202629
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The Contribution Of Rare Variation To Prostate Cancer Heritability
Authors: Mancuso N.
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, Rand K.A.
, Tandon A.
, Allen A.
, Quinque D.
, Mallick S.
, Li H.
, Stram A.
, Sheng X.
, et al.
.
Source: Nature Genetics, 2016 Jan; 48(1), p. 30-5.
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Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array.
Authors: Bien S.A.
, Wojcik G.L.
, Zubair N.
, Gignoux C.R.
, Martin A.R.
, Kocarnik J.M.
, Martin L.W.
, Buyske S.
, Haessler J.
, Walker R.W.
, et al.
.
Source: Plos One, 2016; 11(12), p. e0167758.
EPub date: 2016-12-14 00:00:00.0.
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Replication of ZNF804A gene variant associations with risk of heroin addiction.
Authors: Hancock D.B.
, Levy J.L.
, Gaddis N.C.
, Glasheen C.
, Saccone N.L.
, Page G.P.
, Bierut L.J.
, Kral A.H.
, Johnson E.O.
.
Source: Genes, Brain, And Behavior, 2015 Nov; 14(8), p. 635-40.
PMID: 26382569
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Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.
Authors: Hancock D.B.
, Levy J.L.
, Gaddis N.C.
, Glasheen C.
, Saccone N.L.
, Page G.P.
, Hulse G.K.
, Wildenauer D.
, Kelty E.A.
, Schwab S.G.
, et al.
.
Source: Biological Psychiatry, 2015-10-01 00:00:00.0; 78(7), p. 474-84.
EPub date: 2015-10-01 00:00:00.0.
PMID: 25744370
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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.
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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.
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Pleiotropic and sex-specific effects of cancer GWAS SNPs on melanoma risk in the population architecture using genomics and epidemiology (PAGE) study.
Authors: Kocarnik J.M.
, Park S.L.
, Han J.
, Dumitrescu L.
, Cheng I.
, Wilkens L.R.
, Schumacher F.R.
, Kolonel L.
, Carlson C.S.
, Crawford D.C.
, et al.
.
Source: Plos One, 2015; 10(3), p. e0120491.
EPub date: 2015-03-19 00:00:00.0.
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Association Of Cancer Susceptibility Variants With Risk Of Multiple Primary Cancers: The Population Architecture Using Genomics And Epidemiology Study
Authors: Park S.L.
, Caberto C.P.
, Lin Y.
, Goodloe R.J.
, Dumitrescu L.
, Love S.A.
, Matise T.C.
, Hindorff L.A.
, Fowke J.H.
, Schumacher F.R.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Nov; 23(11), p. 2568-78.
PMID: 25139936
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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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Replication Of Associations Between Gwas Snps And Melanoma Risk In The Population Architecture Using Genomics And Epidemiology (page) Study
Authors: Kocarnik J.M.
, Park S.L.
, Han J.
, Dumitrescu L.
, Cheng I.
, Wilkens L.R.
, Schumacher F.R.
, Kolonel L.
, Carlson C.S.
, Crawford D.C.
, et al.
.
Source: The Journal Of Investigative Dermatology, 2014 Jul; 134(7), p. 2049-52.
PMID: 24480881
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Pleiotropic Effects Of Genetic Risk Variants For Other Cancers On Colorectal Cancer Risk: Page, Gecco And Ccfr Consortia
Authors: Cheng I.
, Kocarnik J.M.
, Dumitrescu L.
, Lindor N.M.
, Chang-Claude J.
, Avery C.L.
, Caberto C.P.
, Love S.A.
, Slattery M.L.
, Chan A.T.
, et al.
.
Source: Gut, 2014 May; 63(5), p. 800-7.
PMID: 23935004
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Variants At Irx4 As Prostate Cancer Expression Quantitative Trait Loci
Authors: Xu X.
, Hussain W.M.
, Vijai J.
, Offit K.
, Rubin M.A.
, Demichelis F.
, Klein R.J.
.
Source: European Journal Of Human Genetics : Ejhg, 2014 Apr; 22(4), p. 558-63.
PMID: 24022300
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Multiancestral Analysis Of Inflammation-related Genetic Variants And C-reactive Protein In The Population Architecture Using Genomics And Epidemiology Study
Authors: Kocarnik J.M.
, Pendergrass S.A.
, Carty C.L.
, Pankow J.S.
, Schumacher F.R.
, Cheng I.
, Durda P.
, Ambite J.L.
, Deelman E.
, Cook N.R.
, et al.
.
Source: Circulation. Cardiovascular Genetics, 2014 Apr; 7(2), p. 178-88.
PMID: 24622110
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Pleiotropy Of Cancer Susceptibility Variants On The Risk Of Non-hodgkin Lymphoma: The Page Consortium
Authors: Lim U.
, Kocarnik J.M.
, Bush W.S.
, Matise T.C.
, Caberto C.
, Park S.L.
, Carlson C.S.
, Deelman E.
, Duggan D.
, Fesinmeyer M.
, et al.
.
Source: Plos One, 2014; 9(3), p. e89791.
PMID: 24598796
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A Prostate Cancer Model Build By A Novel Svm-id3 Hybrid Feature Selection Method Using Both Genotyping And Phenotype Data From Dbgap
Authors: Yüceba¿ S.C.
, Ayd¿n Son Y.
.
Source: Plos One, 2014; 9(3), p. e91404.
PMID: 24651484
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No Evidence Of Interaction Between Known Lipid-associated Genetic Variants And Smoking In The Multi-ethnic Page Population
Authors: Dumitrescu L.
, Carty C.L.
, Franceschini N.
, Hindorff L.A.
, Cole S.A.
, B¿žková P.
, Schumacher F.R.
, Eaton C.B.
, Goodloe R.J.
, Duggan D.J.
, et al.
.
Source: Human Genetics, 2013 Dec; 132(12), p. 1427-31.
PMID: 24100633
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Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk.
Authors: Wang H.
, Taverna D.
, Stram D.O.
, Fortini B.K.
, Cheng I.
, Wilkens L.R.
, Burnett T.
, Makar K.W.
, Lindor N.M.
, Hopper J.L.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 Nov; 22(11), p. 2094-101.
PMID: 24045924
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Genetic Variants Associated With Fasting Glucose And Insulin Concentrations In An Ethnically Diverse Population: Results From The Population Architecture Using Genomics And Epidemiology (page) Study
Authors: Fesinmeyer M.D.
, Meigs J.B.
, North K.E.
, Schumacher F.R.
, B¿žková P.
, Franceschini N.
, Haessler J.
, Goodloe R.
, Spencer K.L.
, Voruganti V.S.
, et al.
.
Source: Bmc Medical Genetics, 2013-09-25 00:00:00.0; 14, p. 98.
PMID: 24063630
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Post-genome-wide Association Study Challenges For Lipid Traits: Describing Age As A Modifier Of Gene-lipid Associations In The Population Architecture Using Genomics And Epidemiology (page) Study
Authors: Dumitrescu L.
, Carty C.L.
, Franceschini N.
, Hindorff L.A.
, Cole S.A.
, B¿žková P.
, Schumacher F.R.
, Eaton C.B.
, Goodloe R.J.
, Duggan D.J.
, et al.
.
Source: Annals Of Human Genetics, 2013 Sep; 77(5), p. 416-25.
PMID: 23808484
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Association Of The Fto Obesity Risk Variant Rs8050136 With Percentage Of Energy Intake From Fat In Multiple Racial/ethnic Populations: The Page Study
Authors: Park S.L.
, Cheng I.
, Pendergrass S.A.
, Kucharska-Newton A.M.
, Lim U.
, Ambite J.L.
, Caberto C.P.
, Monroe K.R.
, Schumacher F.
, Hindorff L.A.
, et al.
.
Source: American Journal Of Epidemiology, 2013-09-01 00:00:00.0; 178(5), p. 780-90.
PMID: 23820787
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Generalization And Dilution Of Association Results From European Gwas In Populations Of Non-european Ancestry: The Page Study
Authors: Carlson C.S.
, Matise T.C.
, North K.E.
, Haiman C.A.
, Fesinmeyer M.D.
, Buyske S.
, Schumacher F.R.
, Peters U.
, Franceschini N.
, Ritchie M.D.
, et al.
.
Source: Plos Biology, 2013 Sep; 11(9), p. e1001661.
PMID: 24068893
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Replication Of Genetic Loci For Ages At Menarche And Menopause In The Multi-ethnic Population Architecture Using Genomics And Epidemiology (page) Study
Authors: Carty C.L.
, Spencer K.L.
, Setiawan V.W.
, Fernandez-Rhodes L.
, Malinowski J.
, Buyske S.
, Young A.
, Jorgensen N.W.
, Cheng I.
, Carlson C.S.
, et al.
.
Source: Human Reproduction (oxford, England), 2013 Jun; 28(6), p. 1695-706.
PMID: 23508249
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Lack Of Associations Of Ten Candidate Coronary Heart Disease Risk Genetic Variants And Subclinical Atherosclerosis In Four Us Populations: The Population Architecture Using Genomics And Epidemiology (page) Study
Authors: Zhang L.
, Buzkova P.
, Wassel C.L.
, Roman M.J.
, North K.E.
, Crawford D.C.
, Boston J.
, Brown-Gentry K.D.
, Cole S.A.
, Deelman E.
, et al.
.
Source: Atherosclerosis, 2013 Jun; 228(2), p. 390-9.
PMID: 23587283
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Trans-ethnic Fine-mapping Of Lipid Loci Identifies Population-specific Signals And Allelic Heterogeneity That Increases The Trait Variance Explained
Authors: Wu Y.
, Waite L.L.
, Jackson A.U.
, Sheu W.H.
, Buyske S.
, Absher D.
, Arnett D.K.
, Boerwinkle E.
, Bonnycastle L.L.
, Carty C.L.
, et al.
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Source: Plos Genetics, 2013 Mar; 9(3), p. e1003379.
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