{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:01:48Z","timestamp":1791046908234,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,10,7]],"date-time":"2003-10-07T00:00:00Z","timestamp":1065484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Susceptibility to breast cancer is likely to be the result of susceptibility alleles in many different genes. In particular, one segregation analysis of breast cancer suggested that disease susceptibility in noncarriers of BRCA1\/2 mutations may be explicable in terms of a polygenic model, with large numbers of susceptibility polymorphisms acting multiplicatively on risk. We considered the implications for such a model on the design of association studies to detect susceptibility polymorphisms, in particular the efficacy of utilizing cases with a family history of the disease, together with unrelated controls. Relative to a standard case\u2010control association study with cases unselected for family history, the sample size required to detect a common disease susceptibility allele was typically reduced by more than twofold if cases with an affected first\u2010degree relative were selected, and by more than fourfold if cases with two affected first\u2010degree relatives were utilized. The relative efficiency obtained by using familial cases was greater for rarer alleles. Analysis of extended families indicated that the power was most dependent on the immediate (first\u2010degree) family history. Bilateral cases may offer a similar gain in power to cases with two affected first\u2010degree relatives. In contrast to the strong effect of family history, varying the ages at diagnosis of the cases across the range of 35\u201365 years did not strongly affect the power to detect association. These results indicate that association studies based on cases with a strong family history, identified for example through cancer genetics clinics, may be substantially more efficient than population\u2010based studies. <jats:italic>Genet Epidemiol<\/jats:italic> 25: 190\u2013202, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gepi.10261","type":"journal-article","created":{"date-parts":[[2003,10,10]],"date-time":"2003-10-10T22:58:52Z","timestamp":1065826732000},"page":"190-202","source":"Crossref","is-referenced-by-count":194,"title":["Polygenic inheritance of breast cancer: Implications for design of association studies"],"prefix":"10.1002","volume":"25","author":[{"given":"Antonis C.","family":"Antoniou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Easton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,10,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1014"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600008"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001775"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ng879","article-title":"Low\u2010penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCAl or BRCA2 mutations","volume":"31","author":"CHEK2\u2010Breast Cancer Consortium","year":"2002","journal-title":"Nat Genet"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06524-2"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/318187"},{"key":"e_1_2_1_8_1","first-page":"843","article-title":"A systematic review of genetic polymorphisms and breast cancer risk","volume":"8","author":"Dunning AM","year":"1999","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr6"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jncimonographs.a024223"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/81691"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35057062"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/35057149"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.12.1399"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/genetics\/147.3.1423","article-title":"An approximate model of polygenic inheritance","volume":"147","author":"Lange K","year":"1997","journal-title":"Genetics"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21750-5"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370050611"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.19.11389"},{"key":"e_1_2_1_19_1","first-page":"203","volume-title":"Cancer incidence in defined populations. Banbury report 4","author":"Peto J","year":"1980"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/82533"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng853"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077207"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"l","DOI":"10.1086\/321275","article-title":"Linkage disequilibrium in humans: models and data","volume":"69","author":"Pritchard JK","year":"2001","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_24_1","first-page":"222","article-title":"Linkage strategies for genetically complex traits. I. Multilocus models","volume":"46","author":"Risch N","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_25_1","first-page":"733","article-title":"The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches","volume":"10","author":"Risch N","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5281.1516"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","unstructured":"RischN TengJ.1998.The relative power of family\u2010based and case\u2010control designs for linkage disequilibrium studies of complex human diseases. I. DNA pooling. 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