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Ancestry-shift refi...
Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
- Article/chapterEnglish2010
Publisher, publication year, extent ...
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2010-07-22
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Public Library of Science,2010
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-35468
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-35468URI
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https://doi.org/10.1371/journal.pgen.1001029DOI
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https://lup.lub.lu.se/record/1677328URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:121099683URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Sulem, Patrick
(author)
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Zanon, Carlo
(author)
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Gudjonsson, Sigurjon A
(author)
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Thorleifsson, Gudmar
(author)
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Helgason, Agnar
(author)
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Jonasdottir, Aslaug
(author)
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Besenbacher, Soren
(author)
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Kostic, Jelena P
(author)
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Fackenthal, James D
(author)
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Huo, Dezheng
(author)
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Adebamowo, Clement
(author)
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Ogundiran, Temidayo
(author)
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Olson, Janet E
(author)
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Fredericksen, Zachary S
(author)
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Wang, Xianshu
(author)
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Look, Maxime P
(author)
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Sieuwerts, Anieta MKarolinska Institutet
(author)
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Martens, John W M
(author)
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Pajares, Isabel
(author)
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Garcia-Prats, Maria D
(author)
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Ramon-Cajal, Jose M
(author)
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de Juan, Ana
(author)
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Panadero, Angeles
(author)
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Ortega, Eugenia
(author)
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Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-khk
(author)
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Vermeulen, Sita H
(author)
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Asadzadeh, Fatemeh
(author)
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van Engelenburg, K C Anton
(author)
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Margolin, Sara
(author)
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Shen, Chen-Yang
(author)
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Wu, Pei-Ei
(author)
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Försti, AstaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-asf
(author)
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Lenner, PerUmeå universitet,Onkologi(Swepub:umu)pele0005
(author)
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Henriksson, RogerUmeå universitet,Onkologi(Swepub:umu)rohe0003
(author)
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Johansson, RobertUmeå universitet,Onkologi(Swepub:umu)rojo0001
(author)
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Enquist, KerstinUmeå universitet,Näringsforskning
(author)
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Hallmans, GöranUmeå universitet,Näringsforskning(Swepub:umu)goha0001
(author)
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Jonsson, Thorvaldur
(author)
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Sigurdsson, Helgi
(author)
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Alexiusdottir, Kristin
(author)
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Gudmundsson, Julius
(author)
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Sigurdsson, Asgeir
(author)
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Frigge, Michael L
(author)
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Gudmundsson, Larus
(author)
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Kristjansson, Kristleifur
(author)
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Halldorsson, Bjarni V
(author)
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Styrkarsdottir, Unnur
(author)
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Gulcher, Jeffrey R
(author)
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Hemminki, Kari
(author)
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Lindblom, AnnikaKarolinska Institutet
(author)
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Kiemeney, Lambertus A
(author)
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Mayordomo, Jose I
(author)
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Foekens, John A
(author)
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Couch, Fergus J
(author)
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Olopade, Olufunmilayo I
(author)
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Gudbjartsson, Daniel F
(author)
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Thorsteinsdottir, Unnur
(author)
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Rafnar, Thorunn
(author)
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Johannsson, Oskar T
(author)
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Stefansson, Kari
(author)
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Karolinska InstitutetAllmänmedicin och klinisk epidemiologi
(creator_code:org_t)
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In:PLoS genetics: Public Library of Science6:7, s. e1001029-1553-7404
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Stacey, Simon N
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Sulem, Patrick
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Zanon, Carlo
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Gudjonsson, Sigu ...
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Helgason, Agnar
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Jonasdottir, Asl ...
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Kostic, Jelena P
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Fackenthal, Jame ...
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Huo, Dezheng
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Adebamowo, Cleme ...
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Ogundiran, Temid ...
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Olson, Janet E
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Fredericksen, Za ...
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Wang, Xianshu
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Look, Maxime P
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Sieuwerts, Aniet ...
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Martens, John W ...
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Pajares, Isabel
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Garcia-Prats, Ma ...
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Ramon-Cajal, Jos ...
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de Juan, Ana
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Panadero, Angele ...
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Ortega, Eugenia
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Hemminki, Kari
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Vermeulen, Sita ...
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Asadzadeh, Fatem ...
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van Engelenburg, ...
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Margolin, Sara
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Shen, Chen-Yang
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Wu, Pei-Ei
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Försti, Asta
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Lenner, Per
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Henriksson, Roge ...
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Johansson, Rober ...
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Enquist, Kerstin
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Hallmans, Göran
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Jonsson, Thorval ...
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Sigurdsson, Helg ...
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Alexiusdottir, K ...
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Gudmundsson, Jul ...
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Sigurdsson, Asge ...
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Frigge, Michael ...
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Gudmundsson, Lar ...
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Kristjansson, Kr ...
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Halldorsson, Bja ...
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Styrkarsdottir, ...
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Gulcher, Jeffrey ...
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Lindblom, Annika
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Kiemeney, Lamber ...
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Mayordomo, Jose ...
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Foekens, John A
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Couch, Fergus J
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Olopade, Olufunm ...
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Thorsteinsdottir ...
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Rafnar, Thorunn
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Stefansson, Kari
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PLoS genetics
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Umeå University
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Lund University
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Karolinska Institutet