{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T19:10:20Z","timestamp":1700075420152},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,6,23]],"date-time":"2006-06-23T00:00:00Z","timestamp":1151020800000},"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":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Most tests of association between DNA sequence variation and quantitative phenotypes in samples of randomly chosen individuals rely on specification of genotypic strata followed by comparison of phenotypes across these strata. This strategy often succeeds when phenotypic differences are caused by one or two single nucleotide polymorphisms (SNPs) among the surveyed markers. However, when multiple\u2010SNP haplotypes account for observed phenotypic variation, identification of the best partitioning requires examination of an inordinate number of SNP combinations. An alternative approach is to rank individuals by their phenotypic measures and ask whether attributes of the genotypic variation show a non\u2010random distribution along this phenotypic ranking. One simple version of this strategy selects the top and bottom tails of the distribution, and then tests whether genotypes from these two samples are drawn from a single population. This framework does not require the recovery of phased haplotypes and allows contrasts between large numbers of sites at once. We use a method based on this approach to identify associations between plasma triglyceride level, a risk factor for cardiovascular disease, and multi\u2010site genotypes located in the <jats:italic>APOA1\/C3\/A4\/A5<\/jats:italic> cluster of apolipoprotein genes in unrelated individuals (1,071 African\u2010American females, 780 African\u2010American males, 1,036 European\u2010American females, and 930 European\u2010American males) sampled from four US cities as part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Method performance is investigated using simulations that model genealogical variation and different genetic architectures. Results indicate that this multi\u2010site test can identify genotype\u2010phenotype associations with reasonable power, including those generated by some simple epistatic models. <jats:italic>Genet. Epidemiol<\/jats:italic>. 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gepi.20163","type":"journal-article","created":{"date-parts":[[2006,6,27]],"date-time":"2006-06-27T11:36:29Z","timestamp":1151408189000},"page":"508-518","source":"Crossref","is-referenced-by-count":3,"title":["Contrasting multi\u2010site genotypic distributions among discordant quantitative phenotypes: the <i>APOA1\/C3\/A4\/A5<\/i> gene cluster and cardiovascular disease risk factors"],"prefix":"10.1002","volume":"30","author":[{"given":"Bret A.","family":"Payseur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Hixson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles F.","family":"Sing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,23]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)00031-9"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2003.10.003"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.1.252"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1994.tb00733.x"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02623"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20025"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099870"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20006"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00222881"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672302005578"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000099881.83261.D4"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0465-4"},{"key":"e_1_2_1_14_1","volume-title":"Introduction to Quantitative Genetics","author":"Falconer DS","year":"1996"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(88)90080-7"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1106-x"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/134.2.609"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00539-1"},{"key":"e_1_2_1_19_1","first-page":"1","article-title":"Gene genealogies and the coalescent process","volume":"7","author":"Hudson RR","year":"1990","journal-title":"Oxford Surveys Evol Biol"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/155.4.2011"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.2.337"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115175"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.10256"},{"key":"e_1_2_1_24_1","first-page":"125","article-title":"Optimal selection strategies for QTL mapping using pooled DNA samples","volume":"10","author":"Jawaid A","year":"2002","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg255"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.19.6374"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M400437-JLR200"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng917"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300251-JLR200"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.14.2.218"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.9.8.720"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9828"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/420773"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.172901"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064852"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.24.3031"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1086\/321272"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7777857"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/35075590"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.166.1.505"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/321201"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.10246"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg930"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh069"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.24.3039"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-294X.2003.02041.x"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8817.2003.00058.x"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1086\/303068"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(86)29064-3"},{"key":"e_1_2_1_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1949.tb02451.x"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.031799"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1270"}],"container-title":["Genetic Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgepi.20163","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.20163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T18:37:59Z","timestamp":1700073479000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gepi.20163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,23]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1002\/gepi.20163"],"URL":"https:\/\/doi.org\/10.1002\/gepi.20163","archive":["Portico"],"relation":{},"ISSN":["0741-0395","1098-2272"],"issn-type":[{"value":"0741-0395","type":"print"},{"value":"1098-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,23]]}}}