Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls

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Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls


نویسنده	mclaren p.j. ,coulonges c. ,ripke s. ,van den berg l. ,buchbinder s. ,carrington m. ,cossarizza a. ,dalmau j. ,deeks s.g. ,delaneau o. ,de luca a. ,goedert j.j. ,haas d. ,herbeck j.t. ,kathiresan s. ,kirk g.d. ,lambotte o. ,luo m. ,mallal s. ,van manen d. ,martinez-picado j. ,meyer l. ,ap-hp hopital bicêtre ,miro j.m. ,mullins j.i. ,obel n. ,o'brien s.j. ,pereyra f. ,plummer f.a. ,poli g. ,qi y. ,rucart p. ,sandhu m.s. ,shea p.r. ,schuitemaker h. ,theodorou i. ,vannberg f. ,veldink j. ,walker b.d. ,weintrob a. ,winkler c.a. ,wolinsky s. ,telenti a. ,goldstein d.b. ,de bakker p.i.w. ,zagury j.-f. ,fellay j.
منبع	plos pathogens - 2013 - دوره : 9 - شماره : 7
چکیده	Multiple genome-wide association studies (gwas) have been performed in hiv-1 infected individuals,identifying common genetic influences on viral control and disease course. similarly,common genetic correlates of acquisition of hiv-1 after exposure have been interrogated using gwas,although in generally small samples. under the auspices of the international collaboration for the genomics of hiv,we have combined the genome-wide single nucleotide polymorphism (snp) data collected by 25 cohorts,studies,or institutions on hiv-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in note s1 in text s1). after imputation using the 1,000 genomes project reference panel,we tested approximately 8 million common dna variants (snps and indels) for association with hiv-1 acquisition in 6,334 infected patients and 7,247 population samples of european ancestry. initial association testing identified the snp rs4418214,the c allele of which is known to tag the hla-b57:01 and b27:05 alleles,as genome-wide significant (p = 3.6×10-11). however,restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. further analyses including testing recessive genetic models,testing for bulk effects of non-genome-wide significant variants,stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on hiv-1 acquisition (with the exception of ccr5δ32 homozygosity). thus,these data suggest that genetic influences on hiv acquisition are either rare or have smaller effects than can be detected by this sample size.

آدرس	school of life sciences,école polytechnique fédérale de lausanne,lausanne,switzerland,institute of microbiology,university hospital center and university of lausanne,lausanne,switzerland,program in medical and population genetics,broad institute of mit and harvard,cambridge,ma, United States, laboratoire génomique,bioinformatique,et applications,ea4627,chaire de bioinformatique,conservatoire national des arts et métiers,paris,france,anrs genomic group (french agency for research on aids and hepatitis),paris, France, program in medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,center for human genetic research,massachusetts general hospital,harvard medical school,boston,ma, United States, department of neurology,rudolf magnus institute of neuroscience,university medical center utrecht,utrecht, Netherlands, bridge hiv,san francisco department of public health,san francisco,ca, United States, cancer and inflammation program,laboratory of experimental immunology,saic frederick,inc.,frederick national laboratory for cancer research,frederick,md,united states,ragon institute of mgh,mit and harvard,boston,ma, United States, department of surgery,medicine,dentistry and morphological sciences university of modena and reggio emilia school of medicine,modena, Italy, aids research institute irsicaixa,institut d'investigació en ciències de la salut germans trias i pujol,universitat autònoma de barcelona,badalona, Spain, department of medicine,university of california,san francisco,ca, United States, department of statistics,university of oxford,oxford, United Kingdom, university division of infectious diseases,siena university hospital,siena,italy,institute of clinical infectious diseases,università cattolica del sacro cuore,roma, Italy, infections and immunoepidemiology branch,division of cancer epidemiology and genetics,national cancer institute,rockville,md, United States, vanderbilt university school of medicine,nashville,tn, United States, department of microbiology,university of washington,seattle,wa, United States, program in medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,cardiovascular research center and center for human genetic research,massachusetts general hospital,harvard medical school,boston,ma, United States, department of epidemiology,johns hopkins university,baltimore,md, United States, inserm u1012,bicêtre,france,university paris-sud,bicêtre,france,ap-hp,department of internal medicine and infectious diseases,bicêtre hospital,bicêtre, France, department of medical microbiology,university of manitoba,winnipeg,mb,canada,national microbiology laboratory,winnipeg,mb, Canada, institute for immunology and infectious diseases,murdoch university and pathwest,perth, Australia, department of experimental immunology,sanquin research,landsteiner laboratory,center for infectious diseases and immunity amsterdam (cinima),academic medical center of the university of amsterdam,amsterdam,netherlands,crucell holland bv,leiden, Netherlands, aids research institute irsicaixa,institut d'investigació en ciències de la salut germans trias i pujol,universitat autònoma de barcelona,badalona,spain,institució catalana de recerca i estudis avançats (icrea),barcelona, Spain, anrs genomic group (french agency for research on aids and hepatitis),paris,france,inserm,cesp u1018,university paris-sud,umrs 1018, Faculté de Médecine Paris-Sud, epidemiology and public health service,le kremlin bicêtre, France, infectious diseases service. hospital clinic - idibaps,university of barcelona,barcelona, Spain, department of microbiology,university of washington,seattle,wa, United States, department of infectious diseases,the national university hospital,rigshospitalet,copenhagen, Denmark, theodosius dobzhansky center for genome bioinformatics,st. petersburg state university,st. petersburg, Russian Federation, ragon institute of mgh,mit and harvard,boston,ma,united states,division of infectious disease,brigham and women's hospital,harvard medical school,boston,ma, United States, department of medical microbiology,university of manitoba,winnipeg,mb,canada,national microbiology laboratory,winnipeg,mb, Canada, division of immunology,transplantation and infectious diseases,vita-salute san raffaele university,school of medicine and san raffaele scientific institute,milan, Italy, cancer and inflammation program,laboratory of experimental immunology,saic frederick,inc.,frederick national laboratory for cancer research,frederick,md, United States, laboratoire génomique,bioinformatique,et applications,ea4627,chaire de bioinformatique,conservatoire national des arts et métiers,paris,france,anrs genomic group (french agency for research on aids and hepatitis),paris, France, genetic epidemiology group,wellcome trust sanger institute,hinxton,united kingdom,non-communicable disease research group,department of public health and primary care,university of cambridge,cambridge, United Kingdom, center for human genome variation,duke university school of medicine,durham,nc, United States, department of experimental immunology,sanquin research,landsteiner laboratory,center for infectious diseases and immunity amsterdam (cinima),academic medical center of the university of amsterdam,amsterdam,netherlands,crucell holland bv,leiden, Netherlands, anrs genomic group (french agency for research on aids and hepatitis),paris,france,inserm umrs 945,paris, France, school of biology,georgia institute of technology,atlanta,ga, United States, department of neurology,rudolf magnus institute of neuroscience,university medical center utrecht,utrecht, Netherlands, ragon institute of mgh,mit and harvard,boston,ma,united states,howard hughes medical institute,chevy chase,md, United States, infectious disease clinical research program,uniformed services university of the health sciences,bethesda,md, United States, basic research laboratory,molecular genetic epidemiology section,center for cancer research,nci,saic-frederick,inc.,frederick national laboratory,frederick,md, United States, division of infectious diseases,the feinberg school of medicine,northwestern university,chicago,il, United States, institute of microbiology,university hospital center and university of lausanne,lausanne, Switzerland, center for human genome variation,duke university school of medicine,durham,nc, United States, program in medical and population genetics,broad institute of mit and harvard,cambridge,ma,united states,division of genetics brigham and women's hospital,harvard medical school,boston,ma,united states,department of medical genetics,university medical center utrecht,utrecht,netherlands,department of epidemiology,university medical center utrecht,utrecht, Netherlands, laboratoire génomique,bioinformatique,et applications,ea4627,chaire de bioinformatique,conservatoire national des arts et métiers,paris,france,anrs genomic group (french agency for research on aids and hepatitis),paris, France, school of life sciences,école polytechnique fédérale de lausanne,lausanne,switzerland,institute of microbiology,university hospital center and university of lausanne,lausanne, Switzerland



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