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Genome-wide association study of red blood cell traits in Hispanics/Latinos: the Hispanic Community Health Study/Study of Latinos
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نویسنده
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hodonsky c.j. ,jain d. ,schick u.m. ,morrison j.v. ,brown l. ,mchugh c.p. ,schurmann c. ,chen d.d. ,liu y.m. ,auer p.l. ,laurie c.a. ,taylor k.d. ,browning b.l. ,li y. ,papanicolaou g. ,rotter j.i. ,kurita r. ,nakamura y. ,browning s.r. ,loos r.j.f. ,north k.e. ,laurie c.c. ,thornton t.a. ,pankratz n. ,bauer d.e. ,sofer t. ,reiner a.p.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 4
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چکیده
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Prior gwas have identified loci associated with red blood cell (rbc) traits in populations of european,african,and asian ancestry. these studies have not included individuals with an amerindian ancestral background,such as hispanics/latinos,nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. using a custom genotyping array enriched for amerindian ancestral content and 1000 genomes imputation,we performed gwas in 12,502 participants of hispanic community health study and study of latinos (hchs/sol) for hematocrit,hemoglobin,rbc count,rbc distribution width (rdw),and rbc indices. approximately 60% of previously reported rbc trait loci generalized to hchs/sol hispanics/latinos,including african ancestral alpha- and beta-globin gene variants. in addition to the known 3.8kb alpha-globin copy number variant,we identified an amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. we also discovered and replicated three genome-wide significant variants in previously unreported loci for rdw (slc12a2 rs17764730,psmb5 rs941718),and hematocrit (prox1 rs3754140). among the proxy variants at the slc12a2 locus we identified rs3812049,located in a bi-directional promoter between slc12a2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding rna,linc01184,as the likely causal variant. we further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of slc12a2 and linc01184 in human erythroid progenitor cells. together,these results reinforce the importance of genetic study of diverse ancestral populations,in particular hispanics/latinos. © 2017 public library of science. all rights reserved.
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آدرس
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department of epidemiology,university of north carolina gillings school of public health,chapel hill,nc, United States, department of biostatistics,university of washington,seattle,wa, United States, the charles bronfman institute for personalized medicine,icahn school of medicine at mount sinai,new york,ny,united states,the genetics of obesity and related metabolic traits program,the icahn school of medicine at mount sinai,new york,ny,united states,division of public health sciences,fred hutchinson cancer research center,seattle,wa, United States, department of biostatistics,university of washington,seattle,wa, United States, department of biostatistics,university of washington,seattle,wa, United States, department of biostatistics,university of washington,seattle,wa,united states,new york genome center,new york,ny, United States, the charles bronfman institute for personalized medicine,icahn school of medicine at mount sinai,new york,ny,united states,the genetics of obesity and related metabolic traits program,the icahn school of medicine at mount sinai,new york,ny, United States, division of hematology/oncology,boston children's hospital,boston,ma, United States, school of medicine,wake forest university,winston-salem,nc, United States, joseph j. zilber school of public health,university of wisconsin milwaukee,milwaukee,wi, United States, department of biostatistics,university of washington,seattle,wa, United States, institute for translational genomics and population sciences,los angeles biomedical research institute at harbor-ucla medical center,torrance,ca,united states,department of pediatrics,los angeles biomedical research institute at harbor-ucla medical center,torrance,ca, United States, department of medicine,university of washington,seattle,wa, United States, department of genetics,university of north carolina,chapel hill,nc,united states,department of biostatistics,university of north carolina,chapel hill,nc,united states,department of computer science,university of north carolina,chapel hill,nc, United States, division of cardiovascular sciences,national heart,lung,and blood institute,bethesda,md, United States, institute for translational genomics and population sciences,los angeles biomedical research institute at harbor-ucla medical center,torrance,ca,united states,department of pediatrics,los angeles biomedical research institute at harbor-ucla medical center,torrance,ca, United States, research and development department,central blood institute,blood service headquartersese red cross society,tokyo, Japan, cell engineering division,riken bioresource center,tsukuba,ibaraki,japan,comprehensive human sciences,tsukuba university,tsukuba,ibaraki, Japan, department of biostatistics,university of washington,seattle,wa, United States, the charles bronfman institute for personalized medicine,icahn school of medicine at mount sinai,new york,ny,united states,the genetics of obesity and related metabolic traits program,the icahn school of medicine at mount sinai,new york,ny,united states,the mindich child health and development institute,icahn school of medicine at mount sinai,new york,ny, United States, department of epidemiology,university of north carolina gillings school of public health,chapel hill,nc,united states,department of genetics,university of north carolina,chapel hill,nc, United States, department of biostatistics,university of washington,seattle,wa, United States, department of biostatistics,university of washington,seattle,wa, United States, division of laboratory medicine & pathology,university of minnesota,minneapolis,mn, United States, division of hematology/oncology,boston children's hospital,boston,ma,united states,department of pediatric oncology,dana-farber cancer institute,boston,ma,united states,department of pediatrics,harvard medical school and harvard stem cell institute,harvard university,boston,ma, United States, department of biostatistics,university of washington,seattle,wa, United States, division of public health sciences,fred hutchinson cancer research center,seattle,wa, United States
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Authors
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