Genome-wide association study identifies novel breast cancer susceptibility loci
Open accessAbstract
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Easton et al. found five new variants associated with familial breast cancer, but only 3.6% of familial breast cancer is accounted for by those alleles.
“For example, Easton et al.79 found five new variants associated with familial breast cancer, but only 3.6% of familial breast cancer is accounted for by those alleles.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [79]
The Abstract and Discussion identify five novel loci associated with breast cancer risk. The Discussion estimates that they explain 3.6% of the *excess familial risk* of breast cancer, assuming the loci interact multiplicatively—not 3.6% of familial breast cancer cases. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLD differences drive differences in effect size estimates from GWAS across populations in proportion to LD between tagging and causal SNP pairs, even when causal effects are the same.
“These LD differences in turn drive differences in effect size estimates (i.e. predictors) from GWAS across populations in proportion to LD between tagging and causal SNP pairs, even when causal effects are the same35,37–40 (Supplementary Note).”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [37]
The Pattern of risks section reports a smaller odds ratio for rs2981582 in Asian than European populations and says this is consistent with rs2981582 not being the functional variant. The FGFR2 section reports weaker LD in the Asian studies. The paper does not establish that effect-size differences are proportional to LD between tagging and causal SNPs, or that the causal effects are the same across populations; it says the causal variant remains unresolved. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLinkage disequilibrium differentiates marginal effect size estimates for polygenic traits across populations, even when causal variants are the same.
“2) linkage disequilibrium (LD) differentiates marginal effect size estimates for polygenic traits across populations, even when causal variants are the same;”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [37]
The Pattern of risks section (page unavailable) reports a smaller per-allele odds ratio for the FGFR2 marker rs2981582 in Asian than European populations and says this is consistent with the marker not being the functional variant. The FGFR2 and Discussion sections (pages unavailable) describe different LD patterns across populations. These passages support a locus-specific example, but do not establish the claim for polygenic traits generally or demonstrate that the causal variants are the same across populations. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRecent genome-wide association studies have detected SNPs significantly associated with breast cancer, colorectal cancer, type 2 diabetes, and heart disease, among other diseases.
“This idea, combined with the development of efficient methods for surveying large numbers of SNPs, has led to the many recent genome-wide association (GWA) studies that have detected SNPs that are significantly associated with breast cancer79,80, colorectal cancer81,82, type 2 diabetes83–86 and heart disease87,88, among other diseases.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [79]
Humans carry a huge pool of phenotypically-neutral background variation that adds noise to genetic analyses (for example, each person has ~100 loss-of-function variants, most of which are rare in a population).
“Humans carry a huge pool of phenotypically-neutral background variation that adds noise to genetic analyses (for example, each person has ~100 loss-of-function variants, most of which are rare in a population), 152,153”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [152]
Most associations do not involve previous candidate genes; some GWAS results immediately suggest new biological hypotheses, such as CFH in AMD, FGFR2 in breast cancer, and CDKN2A/CDKN2B in T2D.
“2) Most associations do not involve previous candidate genes. In some cases, GWAS results immediately suggest new biological hypotheses— for example, the role of complement factor H in age-related macular degeneration (77–79), FGFR2 in breast cancer (98), and CDKN2A and CDKN2B in T2D (99–101).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [98]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1
Miki, Y., Swensen, J. J., Shattuck-Eidens, D. M., Futreal, P. A., Harshman, K., Tavtigian, S. V., Liu, Q., Cochran, C., Bennett, L. M., Ding, W., et al. (1994) · Science · doi:10.1126/science.7545954 · Cited by 6,069 · see citing works
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858 · see citing works
Antoniou, A., Pharoah, P. D. P., Narod, S., Risch, H. A., Eyfjord, J. E., Hopper, J. L., Loman, N., Olsson, H., Johannsson, O., Borg, Å., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/375033 · Cited by 3,680 · see citing works
Self-citationIdentification of the breast cancer susceptibility gene BRCA2
Wooster, R., Bignell, G. R., Lancaster, J., Swift, S., Seal, S., Mangion, J., Collins, N., Gregory, S. G., Gumbs, C. E., Micklem, G., et al. (1995) · Nature · doi:10.1038/378789a0 · Cited by 3,645 · see citing works
Self-citationGenomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · see citing works
Patterns of somatic mutation in human cancer genomes
Greenman, C. D., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G. R., Davies, H. R., Teague, J. W., Butler, A. P., Stevens, C., et al. (2007) · Nature · doi:10.1038/nature05610 · Cited by 3,062 · see citing works
Self-citationScore Tests for Association between Traits and Haplotypes when Linkage Phase Is Ambiguous
Schaid, D. J., Rowland, C. M., Tines, D. E., Jacobson, R. M., & Poland, G. A. (2002) · The American Journal of Human Genetics · doi:10.1086/338688 · Cited by 1,772 · see citing works
Efficiency and power in genetic association studies
de Bakker, P. I. W., Yelensky, R., Pe’er, I., Gabriel, S., Daly, M. J., & Altshuler, D. (2005) · Nature Genetics · doi:10.1038/ng1669 · Cited by 1,678 · see citing works
The Ensembl genome database project
Hubbard, T. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.38 · Cited by 1,610 · see citing works
Comprehensive human genome amplification using multiple displacement amplification
Dean, F. B., Hosono, S., Fang, L., Wu, X., Faruqi, A. F., Bray-Ward, P., Sun, Z., Zong, Q., Du, Y., Du, J., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082089499 · Cited by 1,467 · see citing works
Whole-Genome Patterns of Common DNA Variation in Three Human Populations
Hinds, D., Stuve, L., Nilsen, G. B., Halperin, E., Eskin, E., Ballinger, D., Frazer, K., & Cox, D. (2005) · Science · doi:10.1126/science.1105436 · Cited by 1,245 · see citing works
Self-citationGenome-wide association study of prostate cancer identifies a second risk locus at 8q24
Yeager, M., Orr, N., Hayes, R. B., Jacobs, K. B., Kraft, P., Wacholder, S., Minichiello, M. J., Fearnhead, P., Yu, K. F., Chatterjee, N., et al. (2007) · Nature Genetics · doi:10.1038/ng2022 · Cited by 1,122 · see citing works
Self-citationThe CHEK2-Breast Cancer Consortium (2002) · Nature Genetics · doi:10.1038/ng879 · Cited by 1,104 · see citing works
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
Rahman, N., Seal, S., Thompson, D. J., Kelly, P. F., Renwick, A., Elliott, A., Reid, S., Spanova, K., Barfoot, R., Chagtai, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1959 · Cited by 1,002 · see citing works
Self-citationVariation is the spice of life
Kruglyak, L., & Nickerson, D. A. (2001) · Nature Genetics · doi:10.1038/85776 · Cited by 912 · see citing works
Polygenic susceptibility to breast cancer and implications for prevention
Pharoah, P. D. P., Antoniou, A. C., Bobrow, M., Zimmern, R. L., Easton, D. F., & Ponder, B. A. J. (2002) · Nature Genetics · doi:10.1038/ng853 · Cited by 898 · see citing works
Self-citationGenome-wide association study identifies a second prostate cancer susceptibility variant at 8q24
Guðmundsson, J., Sulem, P., Manolescu, A. R., Amundadottir, L. T., Gudbjartsson, D. F., Helgason, A., Rafnar, Þ., Bergþorsson, J. Þ., Agnarsson, B. A., Baker, A., et al. (2007) · Nature Genetics · doi:10.1038/ng1999 · Cited by 856 · see citing works
A common variant associated with prostate cancer in European and African populations
Amundadottir, L. T., Sulem, P., Gudmundsson, J., Helgason, A., Baker, A., Agnarsson, B. A., Sigurdsson, A., Benediktsdottir, K. R., Cazier, J.-B., Sainz, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1808 · Cited by 787 · see citing works
Day, N., Oakes, S., Luben, R., Khaw, K., Bingham, S., Welch, A., & Wareham, N. (1999) · Nature · doi:10.17863/cam.89388 · Cited by 780 · see citing works
Self-citationThe Breast Cancer Susceptibility Collaboration (UK), Seal, S., Thompson, D., Renwick, A., Elliott, A., Kelly, P., Barfoot, R., Chagtai, T., Jayatilake, H., Ahmed, M., et al. (2006) · Nature Genetics · doi:10.1038/ng1902 · Cited by 746 · see citing works
Self-citationATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles
Renwick, A., Thompson, D. J., Seal, S., Kelly, P. F., Chagtai, T., Ahmed, M., North, B. V., Jayatilake, H., Barfoot, R., Spanova, K., et al. (2006) · Nature Genetics · doi:10.1038/ng1837 · Cited by 743 · see citing works
Self-citationA common coding variant in CASP8 is associated with breast cancer risk
Cox, A., Dunning, A. M., García‐Closas, M., Balasubramanian, S. P., Reed, M., Pooley, K. A., Scollen, S., Baynes, C., Ponder, B. A. J., Chanock, S. J., et al. (2007) · Nature Genetics · doi:10.1038/ng1981 · Cited by 610 · see citing works
Self-citationCancer Risks and Mortality in Heterozygous ATM Mutation Carriers
Thompson, D. J., Duedal, S., Kirner, J., McGuffog, L., Last, J. I. K., Reiman, A., Byrd, P. J., Taylor, A. M. R., & Easton, D. F. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji141 · Cited by 543 · see citing works
Self-citationA recurrent mutation in PALB2 in Finnish cancer families
Erkko, H., Xia, B., Nikkilä, J., Schleutker, J., Syrjäkoski, K., Mannermaa, A., Kallioniemi, A. H., Pylkäs, K., Karppinen, S., Rapakko, K., et al. (2007) · Nature · doi:10.1038/nature05609 · Cited by 466 · see citing works
Self-citation* (2004) · The American Journal of Human Genetics · doi:10.1086/421251 · Cited by 466 · see citing works
The BOADICEA model of genetic susceptibility to breast and ovarian cancer
Antoniou, A. C., Pharoah, P. D. P., Smith, P., & Easton, D. F. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602175 · Cited by 464 · see citing works
Self-citationHow many more breast cancer predisposition genes are there?
Easton, D. F. (1999) · Breast Cancer Research · doi:10.1186/bcr6 · Cited by 315 · see citing works
Self-citationJang, J., Shin, K., & Park, J.-G. (2001) · PubMed · Cited by 275 · see citing works
EPIC-Norfolk: Study design and characteristics of the cohort
Day, N., Oakes, S., Luben, R., Khaw, K., Bingham, S., Welch, A., & Wareham, N. (1999) · UEA Digital Repository (University of East Anglia) · Cited by 261 · see citing works
Self-citationThe Breast Cancer Association Consortium (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj374 · Cited by 258 · see citing works
Recent developments in genomewide association scans: a workshop summary and review.
Thomas, D. C., Haile, R., & Duggan, D. (2005) · American Journal of Human Genetics · doi:10.1086/432962 · Cited by 247 · see citing works
Adnane, J., Gaudray, P., Ca, D., et al. (1991) · PubMed · Cited by 242 · see citing works
Polygenic inheritance of breast cancer: Implications for design of association studies
Antoniou, A. C., & Easton, D. F. (2003) · Genetic Epidemiology · doi:10.1002/gepi.10261 · Cited by 232 · see citing works
Self-citation20q11.1 amplification in giant‐cell tumor of bone: Array CGH, FISH, and association with outcome
Smith, L. T., Mayerson, J. L., Nowak, N. J., Suster, D. I., Mohammed, N., Long, S., Auer, H., Jones, S., McKeegan, C., Young, G. S., et al. (2006) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20354 · Cited by 112 · see citing works
Two‐Stage Designs for Gene–Disease Association Studies
Satagopan, J. M., Verbel, D., Venkatraman, E. S., Offit, K., & Begg, C. B. (2002) · Biometrics · doi:10.1111/j.0006-341x.2002.00163.x · Cited by 111 · see citing works
Moffa, A. B., Tannheimer, S. L., & Ethier, S. P. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.643.2.11 · Cited by 100 · see citing works
PReMod: a database of genome-wide mammalian cis-regulatory module predictions
Ferretti, V., Poitras, C., Bergeron, D., Coulombe, B., Robert, F., & Blanchette, M. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl879 · Cited by 90 · see citing works
Allelic association of the human homologue of the mouse modifier Ptprj with breast cancer
Lesueur, F., Pharoah, P. D. P., Laing, S., Ahmed, S., Jordan, C., Smith, P. L., Luben, R., Wareham, N. J., Easton, D. F., Dunning, A. M., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi237 · Cited by 73 · see citing works
Self-citationTyrer, J. P., Pharoah, P. D. P., & Easton, D. F. (2006) · Genetic Epidemiology · doi:10.1002/gepi.20175 · Cited by 35 · see citing works
Self-citationA genome wide linkage search for breast cancer susceptibility genes
Smith, P. L., McGuffog, L., Easton, D. F., et al. (2006) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20330 · Cited by 9 · see citing works
Self-citationErratum: Corrigendum: A common coding variant in CASP8 is associated with breast cancer risk
Cox, A., Dunning, A. M., García‐Closas, M., et al. (2007) · Nature Genetics · doi:10.1038/ng0507-688b · Cited by 4 · see citing works
Self-citationErbB-4 dependent proliferation of ER+ breast cells
Davies, M. (1999) · Breast Cancer Research · doi:10.1186/bcr-1999-66628 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Genome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891 · see citing works
Clinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,831 · see citing works
Variance component model to account for sample structure in genome-wide association studies
Kang, H. M., Sul, J. H., Service, S. K., Zaitlen, N. A., Kong, S.-Y., Freimer, N. B., Sabatti, C., & Eskin, E. (2010) · Nature Genetics · doi:10.1038/ng.548 · Cited by 2,817 · see citing works
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279 · see citing works
Self-citationLinkage disequilibrium--understanding the evolutionary past and mapping the medical future.
Slatkin, M. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2361 · Cited by 1,614 · see citing works
Tutt, A., Robson, M., Garber, J. E., Domchek, S. M., Audeh, M. W., Weitzel, J. N., Friedlander, M., Arun, B., Loman, N., Schmutzler, R. K., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60892-6 · Cited by 1,655 · see citing works
Self-citationGenomewide Association Studies and Assessment of the Risk of Disease
Manolio, T. A. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0905980 · Cited by 1,512 · see citing works
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Detecting gene–gene interactions that underlie human diseases
Cordell, H. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2579 · Cited by 1,350 · see citing works
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Wellcome Trust Case Control Consortium, & The Australo-Anglo-American Spondylitis Consortium (TASC) (2007) · Nature Genetics · doi:10.1038/ng.2007.17 · Cited by 1,374 · see citing works
Replicating genotype–phenotype associations
NCI-NHGRI Working Group on Replication in Association Studies, Chanock, S. J., Manolio, T., Boehnke, M., Boerwinkle, E., Hunter, D. J., Thomas, G., Hirschhorn, J. N., Abecasis, G., Altshuler, D., et al. (2007) · Nature · doi:10.1038/447655a · Cited by 1,352 · see citing works
Self-citationGenetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177 · see citing works
Long story short: the serotonin transporter in emotion regulation and social cognition
Canli, T., & Lesch, K.-P. (2007) · Nature Neuroscience · doi:10.1038/nn1964 · Cited by 1,034 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
Little, J., Higgins, J. P. T., Ioannidis, J. P. A., Moher, D., Gagnon, F., von Elm, E., Khoury, M. J., Cohen, B., Davey-Smith, G., Grimshaw, J., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000022 · Cited by 811 · see citing works
Park, J.-H., Wacholder, S., Gail, M. H., Peters, U., Jacobs, K. B., Chanock, S. J., & Chatterjee, N. (2010) · Nature Genetics · doi:10.1038/ng.610 · Cited by 678 · see citing works
Self-citationYang, X. R., Chang-Claude, J., Goode, E. L., Couch, F. J., Nevanlinna, H., Milne, R. L., Gaudet, M., Schmidt, M. K., Broeks, A., Cox, A., et al. (2011) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djq526 · Cited by 691 · see citing works
Self-citationGenome-wide association study identifies five new breast cancer susceptibility loci
The Breast Cancer Susceptibility Collaboration (UK), Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.586 · Cited by 687 · see citing works
Self-citationNew IBD genetics: common pathways with other diseases
Lees, C. W., Barrett, J. C., Parkes, M., & Satsangi, J. (2011) · Gut · doi:10.1136/gut.2009.199679 · Cited by 635 · see citing works
Parental origin of sequence variants associated with complex diseases
DIAGRAM Consortium, Kong, A., Steinthorsdottir, V., Masson, G., Thorleifsson, G., Sulem, P., Besenbacher, S., Jonasdottir, A., Sigurdsson, A., Kristinsson, K. T., et al. (2009) · Nature · doi:10.1038/nature08625 · Cited by 553 · see citing works
Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1
Zheng, W., Long, J., Gao, Y.-T., Li, C., Zheng, Y., Xiang, Y.-B., Wen, W., Levy, S., Deming, S. L., Haines, J. L., et al. (2009) · Nature Genetics · doi:10.1038/ng.318 · Cited by 541 · see citing works
The emerging landscape of breast cancer susceptibility
Stratton, M. R., & Rahman, N. (2008) · Nature Genetics · doi:10.1038/ng.2007.53 · Cited by 487 · see citing works
Self-citationRung, J., Cauchi, S., Albrechtsen, A., Shen, L., Rocheleau, G., Cavalcanti-Proença, C., Bacot, F., Balkau, B., Belisle, A., Borch-Johnsen, K., et al. (2009) · Nature Genetics · doi:10.1038/ng.443 · Cited by 479 · see citing works
Kinase mutations in human disease: interpreting genotype–phenotype relationships
Lahiry, P., Torkamani, A., Schork, N. J., & Hegele, R. A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2707 · Cited by 420 · see citing works
Herranz, D., Ambesi-Impiombato, A., Palomero, T., Schnell, S. A., Belver, L., Wendorff, A. A., Xu, L., Castillo-Martin, M., Llobet-Navás, D., Cordon-Cardo, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3665 · Cited by 405 · see citing works
Lesch, K.-P., Timmesfeld, N., Renner, T. J., Halperin, R., Röser, C., Nguyen, T. T., Craig, D. W., Romanos, J., Heine, M., Meyer, J., et al. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0119-3 · Cited by 374 · see citing works
Goriely, A., & Wilkie, A. O. M. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.12.017 · Cited by 365 · see citing works
Variation near complement factor I is associated with risk of advanced AMD
Fagerness, J. A., Maller, J. B., Neale, B. M., Reynolds, R. C., Daly, M. J., & Seddon, J. M. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.140 · Cited by 357 · see citing works
Sanders, A. R., Duan, J., Levinson, D. F., Shi, J., He, D., Hou, C., Burrell, G. J., Rice, J. P., Nertney, D. A., Olincy, A., et al. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07101573 · Cited by 349 · see citing works
Base excision repair and cancer
Wallace, S. S., Murphy, D. L., & Sweasy, J. B. (2012) · Cancer Letters · doi:10.1016/j.canlet.2011.12.038 · Cited by 329 · see citing works
The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression
Kohli, M. A., Lucae, S., Saemann, P. G., Schmidt, M. V., Demirkan, A., Hek, K., Czamara, D., Alexander, M., Salyakina, D., Ripke, S., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.005 · Cited by 228 · see citing works
The search for genes contributing to endometriosis risk
Montgomery, G. W., Nyholt, D. R., Zhao, Z. Z., Treloar, S. A., Painter, J. N., Missmer, S. A., Kennedy, S. H., & Zondervan, K. T. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn016 · Cited by 211 · see citing works
Genetic association analysis of copy-number variation (CNV) in human disease pathogenesis
Ionita-Laza, I., Rogers, A. J., Lange, C., Raby, B. A., & Lee, C. (2009) · Genomics · doi:10.1016/j.ygeno.2008.08.012 · Cited by 198 · see citing works
Guilt beyond a reasonable doubt
Altshuler, D., & Daly, M. (2007) · Nature Genetics · doi:10.1038/ng0707-813 · Cited by 151 · see citing works
Visscher, P. M., Goddard, M. E., Derks, E. M., & Wray, N. R. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.65 · Cited by 138 · see citing works
Sætrom, P., Biesinger, J., Li, S. M., Smith, D., Thomas, L. F., Majzoub, K., Rivas, G. E., Alluin, J., Rossi, J. J., Krontiris, T. G., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1201 · Cited by 138 · see citing works
Accommodating Linkage Disequilibrium in Genetic-Association Analyses via Ridge Regression
Malo, N., Libiger, O., & Schork, N. J. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.10.012 · Cited by 133 · see citing works
Night work and breast cancer – results from the German GENICA study
Pesch, B., Harth, V., Rabstein, S., Baisch, C., Schiffermann, M., Pallapies, D., Bonberg, N., Heinze, E., Spickenheuer, A., Justenhoven, C., et al. (2010) · Scandinavian Journal of Work, Environment & Health · doi:10.5271/sjweh.2890 · Cited by 132 · see citing works
Self-citationSubtypes of familial breast tumours revealed by expression and copy number profiling
kConFab Investigators, Waddell, N., Arnold, J., Cocciardi, S., da Silva, L., Marsh, A., Riley, J., Johnstone, C. N., Orloff, M., Assie, G., et al. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0653-1 · Cited by 99 · see citing works
Self-citationZhong, H., & Prentice, R. L. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20437 · Cited by 94 · see citing works
Glodzik, D., Morganella, S., Davies, H., Simpson, P. T., Li, Y., Zou, X., Diez-Perez, J., Staaf, J., Alexandrov, L. B., Smid, M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3771 · Cited by 84 · see citing works
Self-citationByrnes, G. B., Southey, M. C., & Hopper, J. L. (2008) · Breast Cancer Research · doi:10.1186/bcr2099 · Cited by 83 · see citing works
Self-citationCai, Q., Wen, W., Qu, S., Li, G., Egan, K. M., Chen, K., Deming, S. L., Shen, H., Shen, C.-Y., Gammon, M. D., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2733 · Cited by 85 · see citing works
Self-citationGenome-wide association studies and the genetic dissection of complex traits
Sebastiani, P., Timofeev, N., Dworkis, D. A., Perls, T. T., & Steinberg, M. H. (2009) · American Journal of Hematology · doi:10.1002/ajh.21440 · Cited by 67 · see citing works
Solyom, S., Aressy, B., Pylkäs, K., Patterson-Fortin, J., Hartikainen, J. M., Kallioniemi, A., Kauppila, S., Nikkilä, J., Kosma, V.-M., Mannermaa, A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003223 · Cited by 59 · see citing works
The ‘Common Disease-Common Variant’ Hypothesis and Familial Risks
Hemminki, K., Försti, A., & Bermejo, J. L. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002504 · Cited by 57 · see citing works
Glycomics meets genomics, epigenomics and other high throughput omics for system biology studies
Zoldoš, V., Horvat, T., & Lauc, G. (2013) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.12.007 · Cited by 56 · see citing works
Hwang, J.-Y., Lee, S. H., Kim, G. S., Koh, J.-M., Go, M. J., Kim, Y.-J., Kim, H.-C., Kim, T.-H., Hong, J. M., Park, E. K., et al. (2009) · Bone · doi:10.1016/j.bone.2009.07.080 · Cited by 55 · see citing works
Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment
Scaife, J. E., Barnett, G. C., Noble, D. J., Jena, R., Thomas, S. J., West, C. M. L., & Burnet, N. G. (2015) · The British Journal of Radiology · doi:10.1259/bjr.20150172 · Cited by 53 · see citing works
Current clinical use of polygenic scores will risk exacerbating health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2018) · doi:10.1101/441261 · Cited by 2,813 · see citing works
Metafuni, E., Chiusolo, P., Laurenti, L., Sorà, F., Giammarco, S., Bacigalupo, A., Leone, G., & Sica, S. (2018) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2018.005 · Cited by 14 · see citing works
- Authors
- Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., Wareham, N., Ahmed, S., Healey, C. S., Bowman, R., collaborators, T. S., Luccarini, C., Conroy, D., Shah, M., Munday, H., Jordan, C., Perkins, B., West, J., Redman, K., Driver, K., Meyer, K. B., Haiman, C. A., Kolonel, L. K., Henderson, B. E., Le Marchand, L., Brennan, P., Sangrajrang, S., Gaborieau, V., Odefrey, F., Shen, C.-Y., Wu, P.-E., Wang, H.-C., Eccles, D., Evans, D. G., Peto, J., Fletcher, O., Johnson, N., Seal, S., Stratton, M. R., Rahman, N., Chenevix-Trench, G., Bojesen, S. E., Nordestgaard, B. G., Axelsson, C. K., Garcia-Closas, M., Brinton, L., Chanock, S., Lissowska, J., Peplonska, B., Nevanlinna, H., Fagerholm, R., Eerola, H., Kang, D., Yoo, K.-Y., Noh, D.-Y., Ahn, S.-H., Hunter, D. J., Hankinson, S. E., Cox, D. G., Hall, P., Wedren, S., Liu, J., Low, Y.-L., Bogdanova, N., Schürmann, P., Dörk, T., Tollenaar, R. A. E. M., Jacobi, C. E., Devilee, P., Klijn, J. G. M., Sigurdson, A. J., Doody, M. M., Alexander, B. H., Zhang, J., Cox, A., Brock, I. W., MacPherson, G., Reed, M. W. R., Couch, F. J., Goode, E. L., Olson, J. E., Meijers-Heijboer, H., van den Ouweland, A., Uitterlinden, A., Rivadeneira, F., Milne, R. L., Ribas, G., Gonzalez-Neira, A., Benitez, J., Hopper, J. L., McCredie, M., Southey, M., Giles, G. G., Schroen, C., Justenhoven, C., Brauch, H., Hamann, U., Ko, Y.-D., Spurdle, A. B., Beesley, J., Chen, X., kConFab, Aghmesheh, M., Amor, D., Andrews, L., Antill, Y., Armes, J., Armitage, S., Arnold, L., Balleine, R., Begley, G., Beilby, J., Bennett, I., Bennett, B., Berry, G., Blackburn, A., Brennan, M., Brown, M., Buckley, M., Burke, J., Butow, P., Byron, K., Callen, D., Campbell, I., Chenevix-Trench, G., Clarke, C., Colley, A., Cotton, D., Cui, J., Culling, B., Cummings, M., Dawson, S.-J., Dixon, J., Dobrovic, A., Dudding, T., Edkins, T., Eisenbruch, M., Farshid, G., Fawcett, S., Field, M., Firgaira, F., Fleming, J., Forbes, J., Friedlander, M., Gaff, C., Gardner, M., Gattas, M., George, P., Giles, G., Gill, G., Goldblatt, J., Greening, S., Grist, S., Haan, E., Harris, M., Hart, S., Hayward, N., Hopper, J., Humphrey, E., Jenkins, M., Jones, A., Kefford, R., Kirk, J., Kollias, J., Kovalenko, S., Lakhani, S., Leary, J., Lim, J., Lindeman, G., Lipton, L., Lobb, L., Maclurcan, M., Mann, G., Marsh, D., McCredie, M., McKay, M., Anne McLachlan, S., Meiser, B., Milne, R., Mitchell, G., Newman, B., O’Loughlin, I., Osborne, R., Peters, L., Phillips, K., Price, M., Reeve, J., Reeve, T., Richards, R., Rinehart, G., Robinson, B., Rudzki, B., Salisbury, E., Sambrook, J., Saunders, C., Scott, C., Scott, E., Scott, R., Seshadri, R., Shelling, A., Southey, M., Spurdle, A., Suthers, G., Taylor, D., Tennant, C., Thorne, H., Townshend, S., Tucker, K., Tyler, J., Venter, D., Visvader, J., Walpole, I., Ward, R., Waring, P., Warner, B., Warren, G., Watson, E., Williams, R., Wilson, J., Winship, I., Young, M. A., AOCS Management Group, Bowtell, D., Green, A., deFazio, A., Chenevix-Trench, G., Gertig, D., Webb, P., Mannermaa, A., Kosma, V.-M., Kataja, V., Hartikainen, J., Day, N. E., Cox, D. R., & Ponder, B. A. J.
- Affiliations
- University of Cambridge (GB)
- Cancer Research UK (GB)
- Perlegen (United States) (US)
- National Cancer Institute (US)
- University of Southern California (US)
- National Cancer Institute of Thailand (TH)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Princess Anne Hospital (GB)
- Institute of Cancer Research (GB)
- University of Copenhagen (DK)
- National Institutes of Health (US)
- Nofer Institute of Occupational Medicine (PL)
- Helsinki University Hospital (FI)
- Seoul National University (KR)
- Brigham and Women's Hospital (US)
- Royal Children's Hospital (AU)
- Karolinska Institutet (SE)
- Genome Institute of Singapore (SG)
- Medizinische Hochschule Hannover (DE)
- Leiden University Medical Center (NL)
- United States Department of Health and Human Services (US)
- University of Minnesota (US)
- University of Sheffield (GB)
- Mayo Clinic (US)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Erasmus University Rotterdam (NL)
- Spanish National Cancer Research Centre (ES)
- The University of Melbourne (AU)
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology (DE)
- German Cancer Research Center (DE)
- QIMR Berghofer Medical Research Institute (AU)
- Prince of Wales Hospital (AU)
- Royal Women's Hospital (AU)
- Royal Brisbane and Women's Hospital (AU)
- Westmead Hospital (AU)
- Queen Elizabeth II Medical Centre (AU)
- The University of Sydney (AU)
- Australian National University (AU)
- The University of Queensland (AU)
- Royal Prince Alfred Hospital (AU)
- The Royal Melbourne Hospital (AU)
- Peter MacCallum Cancer Centre (AU)
- Wellington Hospital (NZ)
- Princess Margaret Hospital for Children (AU)
- South Australia Pathology (AU)
- Monash Medical Centre (AU)
- Griffith University (AU)
- Flinders Medical Centre (AU)
- Cancer Council Victoria (AU)
- Royal Adelaide Hospital (AU)
- King Edward Memorial Hospital (AU)
- Women's and Children's Hospital (AU)
- Royal North Shore Hospital (AU)
- Edith Cowan University (AU)
- Queensland University of Technology (AU)
- University of Otago (NZ)
- Christchurch Hospital (NZ)
- University of Auckland (NZ)
- Royal Perth Hospital (AU)
- Cabrini Hospital (AU)
- St Vincent's Hospital Sydney (AU)
- Corresponding author
- Easton, Douglas F.
- ORCID
- Easton, Douglas F.
- Pooley, Karen A.
- Dunning, Alison M.
- Pharoah, Paul D. P.
- Thompson, Deborah
- Struewing, Jeffery P.
- Luben, Robert
- Wareham, Nicholas
- Ahmed, Shahana
- Bowman, Richard
- Luccarini, Craig
- Shah, Mitul
- Meyer, Kerstin B.
- Brennan, Paul
- Sangrajrang, Suleeporn
- Shen, Chen-Yang
- Wu, Pei-Ei
- Wang, Hui-Chun
- Eccles, Diana
- Evans, D. Gareth
- Peto, Julian
- Fletcher, Olivia
- Johnson, Nichola
- Stratton, Michael R.
- Rahman, Nazneen
- Bojesen, Stig E.
- Nordestgaard, Børge G.
- Brinton, Louise
- Chanock, Stephen
- Lissowska, Jolanta
- Nevanlinna, Heli
- Kang, Daehee
- Noh, Dong-Young
- Ahn, Sei-Hyun
- Hunter, David J.
- Hankinson, Susan E.
- Cox, David G.
- Hall, Per
- Liu, Jianjun
- Bogdanova, Natalia
- Dörk, Thilo
- Tollenaar, Rob A. E. M.
- Devilee, Peter
- Alexander, Bruce H.
- Zhang, Jinghui
- Cox, Angela
- Reed, Malcolm W. R.
- Couch, Fergus J.
- Goode, Ellen L.
- Olson, Janet E.
- Meijers-Heijboer, Hanne
- Uitterlinden, André
- Rivadeneira, Fernando
- Benitez, Javier
- Justenhoven, Christina
- Brauch, Hiltrud
- Hamann, Ute
- Aghmesheh, Morteza
- Amor, David
- Andrews, Lesley
- Antill, Yoland
- Balleine, Rosemary
- Beilby, John
- Bennett, Ian
- Blackburn, Anneke
- Brennan, Meagan
- Brown, Melissa
- Buckley, Michael
- Burke, Jo
- Butow, Phyllis
- Callen, David
- Campbell, Ian
- Clarke, Christine
- Cummings, Margaret
- Dawson, Sarah-Jane
- Dobrovic, Alexander
- Dudding, Tracy
- Eisenbruch, Maurice
- Farshid, Gelareh
- Field, Michael
- Forbes, John
- Friedlander, Michael
- Gaff, Clara
- Haan, Eric
- Jenkins, Mark
- Lakhani, Sunil
- Lim, Jacqueline
- Lipton, Lara
- Mann, Graham
- Marsh, Deborah
- Meiser, Bettina
- Osborne, Richard
- Richards, Robert
- Robinson, Bridget
- Saunders, Christobel
- Scott, Clare
- Scott, Elizabeth
- Scott, Rodney
- Shelling, Andrew
- Suthers, Graeme
- Taylor, Donna
- Tennant, Christopher
- Thorne, Heather
- Tucker, Kathy
- Visvader, Jane
- Waring, Paul
- Winship, Ingrid
- Bowtell, David
- deFazio, Anna
- Kosma, Veli-Matti
- Kataja, Vesa
- Hartikainen, Jaana
- Cox, David R.
- Venue
- Nature
- Published
- 2007-06-28
- Volume
- 447
- Issue
- 7148
- Pages
- 1087-1093
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2714974
- OpenAlex
- W1994664175
- Cited by
- 2,319
- References
- 43
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 31 · 2023: 52 · 2022: 24 · 2021: 58 · 2020: 60 · 2019: 73 · 2018: 75 · 2017: 86 · 2016: 102 · 2015: 109 · 2014: 134 · 2013: 171 · 2012: 173
- FWCI
- 168.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Australasian Journal of Paramedicine (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- University Libraries (University of Maryland) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Figshare (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Griffith Research Online (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Digital Repository at the University of Maryland (University of Maryland College Park)
- Funders
- Wellcome Trust (999998)
- ACT Government
- Cancer Research UK (A3353)
- Curtin University of Technology
- Peter MacCallum Cancer Centre
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- breast cancer, genetic susceptibility, genetic susceptibility loci, single nucleotide polymorphisms, FGFR2, MAP3K1, LSP1, familial aggregation, risk classification, disease prevention
- MeSH terms
- Alleles, Asia, Southeastern, Australia, Breast Neoplasms, Europe, Female, Genotype, High Mobility Group Proteins, Humans, Microfilament Proteins, North America, Receptors, Progesterone, Trans-Activators, Genome, Human, Odds Ratio, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, MAP Kinase Kinase Kinase 1, Apoptosis Regulatory Proteins, Receptor, Fibroblast Growth Factor, Type 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
