{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T10:37:57Z","timestamp":1722681477964},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T00:00:00Z","timestamp":1341446400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002600","type":"journal-article","created":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T01:17:14Z","timestamp":1341537434000},"page":"e1002600","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Predicting Signatures of \u201cSynthetic Associations\u201d and \u201cNatural Associations\u201d from Empirical Patterns of Human Genetic Variation"],"prefix":"10.1371","volume":"8","author":[{"given":"Diana","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Keinan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2012,7,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1093\/hmg\/11.20.2417","article-title":"The allelic architecture of human disease genes: common disease-common variant\u2026or not?","volume":"11","author":"JK Pritchard","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1371\/journal.pgen.0040033","article-title":"What can genome-wide association studies tell us about the genetics of common disease?","volume":"4","author":"MM Iles","year":"2008","journal-title":"PLoS Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0168-9525(01)02410-6","article-title":"On the allelic spectrum of human disease.","volume":"17","author":"DE Reich","year":"2001","journal-title":"Trends Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrg2554","article-title":"Human genetic variation and its contribution to complex traits.","volume":"10","author":"KA Frazer","year":"2009","journal-title":"Nat Rev Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nature08494","article-title":"Finding the missing heritability of complex diseases.","volume":"461","author":"TA Manolio","year":"2009","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/456018a","article-title":"Personal genomes: The case of the missing heritability.","volume":"456","author":"B Maher","year":"2008","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrg2809","article-title":"Missing heritability and strategies for finding the underlying causes of complex disease.","volume":"11","author":"EE Eichler","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ng.f.136","article-title":"Common and rare variants in multifactorial susceptibility to common diseases.","volume":"40","author":"W Bodmer","year":"2008","journal-title":"Nat Genet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1086\/321272","article-title":"Are rare variants responsible for susceptibility to complex diseases?","volume":"69","author":"JK Pritchard","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nrg2344","article-title":"Genome-wide association studies for complex traits: consensus, uncertainty and challenges.","volume":"9","author":"MI McCarthy","year":"2008","journal-title":"Nat Rev Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ajhg.2010.04.003","article-title":"Interpretation of association signals and identification of causal variants from genome-wide association studies.","volume":"86","author":"K Wang","year":"2010","journal-title":"Am J Hum Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg2779","article-title":"Uncovering the roles of rare variants in common disease through whole-genome sequencing.","volume":"11","author":"ET Cirulli","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1000294","DOI":"10.1371\/journal.pbio.1000294","article-title":"Rare variants create synthetic genome-wide associations.","volume":"8","author":"SP Dickson","year":"2010","journal-title":"PLoS Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"R156","DOI":"10.1093\/hmg\/ddn289","article-title":"Genome-wide association studies: potential next steps on a genetic journey.","volume":"17","author":"MI McCarthy","year":"2008","journal-title":"Hum Mol Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nrg2760","article-title":"Genome-wide association studies in diverse populations.","volume":"11","author":"NA Rosenberg","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrg2867","article-title":"Statistical analysis strategies for association studies involving rare variants.","volume":"11","author":"V Bansal","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrneurol.2010.91","article-title":"Multiple sclerosis genetics\u2013is the glass half full, or half empty?","volume":"6","author":"JR Oksenberg","year":"2010","journal-title":"Nat Rev Neurol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e13584","DOI":"10.1371\/journal.pone.0013584","article-title":"Comprehensive Approach to Analyzing Rare Genetic Variants.","volume":"5","author":"TJ Hoffmann","year":"2010","journal-title":"PLoS ONE"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e14318","DOI":"10.1371\/journal.pone.0014318","article-title":"Three ways of combining genotyping and resequencing in case-control association studies.","volume":"5","author":"JA Longmate","year":"2010","journal-title":"PloS ONE"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","article-title":"Rare-variant association testing for sequencing data with the sequence kernel association test.","volume":"89","author":"MC Wu","year":"2011","journal-title":"Am J Hum Genet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e1000384","DOI":"10.1371\/journal.pgen.1000384","article-title":"A groupwise association test for rare mutations using a weighted sum statistic.","volume":"5","author":"BE Madsen","year":"2009","journal-title":"PLoS Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.ajhg.2010.04.005","article-title":"Pooled association tests for rare variants in exon-resequencing studies.","volume":"86","author":"AL Price","year":"2010","journal-title":"Am J Hum Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1159\/000288704","article-title":"A data-adaptive sum test for disease association with multiple common or rare variants.","volume":"70","author":"F Han","year":"2010","journal-title":"Hum Hered"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1101\/gr.115832.110","article-title":"Detection of common single nucleotide polymorphisms synthesizing quantitative trait association of rarer causal variants.","volume":"21","author":"F Takeuchi","year":"2011","journal-title":"Genome Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nature08825","article-title":"ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.","volume":"464","author":"J Fellay","year":"2010","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1474-4422(10)70197-6","article-title":"Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study.","volume":"9","author":"A Shatunov","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1056\/NEJMoa054013","article-title":"Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.","volume":"354","author":"JC Cohen","year":"2006","journal-title":"New Engl J Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng1984","article-title":"Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.","volume":"39","author":"S Romeo","year":"2007","journal-title":"Nat Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ng.291","article-title":"Common variants at 30 loci contribute to polygenic dyslipidemia.","volume":"41","author":"S Kathiresan","year":"2009","journal-title":"Nat Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.","volume":"447","year":"2007","journal-title":"Nature"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1053\/gast.2003.50045","article-title":"The genetics of inflammatory bowel disease.","volume":"124","author":"DK Bonen","year":"2003","journal-title":"Gastroenterology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn&apos;s disease.","volume":"411","author":"JP Hugot","year":"2001","journal-title":"Nature"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn&apos;s disease.","volume":"411","author":"Y Ogura","year":"2001","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1093\/hmg\/ddq368","article-title":"Synthetic associations in the context of genome-wide association scan signals.","volume":"19","author":"G Orozco","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1000580","DOI":"10.1371\/journal.pbio.1000580","article-title":"Synthetic associations are unlikely to account for many common disease genome-wide association signals.","volume":"9","author":"CA Anderson","year":"2011","journal-title":"PLoS Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e1000579","DOI":"10.1371\/journal.pbio.1000579","article-title":"Synthetic associations created by rare variants do not explain most GWAS results.","volume":"9","author":"NR Wray","year":"2011","journal-title":"PLoS Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000073729","article-title":"Detecting disease associations due to linkage disequilibrium using haplotype tags: a class of tests and the determinants of statistical power.","volume":"56","author":"JM Chapman","year":"2003","journal-title":"Hum Hered"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ncomms1130","article-title":"Deep resequencing reveals excess rare recent variants consistent with explosive population growth.","volume":"1","author":"A Coventry","year":"2010","journal-title":"Nat Commun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1126\/science.1217283","article-title":"Recent explosive human population growth has resulted in an excess of rare genetic variants.","volume":"336","author":"A Keinan","year":"2012","journal-title":"Science"},{"key":"ref40","article-title":"Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes.","author":"JA Tennessen","year":"2012","journal-title":"Science"},{"key":"ref41","article-title":"An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People.","author":"MR Nelson","year":"2012","journal-title":"Science"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/35075590","article-title":"Linkage disequilibrium in the human genome.","volume":"411","author":"DE Reich","year":"2001","journal-title":"Nature"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1086\/316906","article-title":"The extent of linkage disequilibrium in four populations with distinct demographic histories.","volume":"67","author":"AM Dunning","year":"2000","journal-title":"Am J Hum Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.271.5254.1380","article-title":"Global patterns of linkage disequilibrium at the CD4 locus and modern human origins.","volume":"271","author":"S Tishkoff","year":"1996","journal-title":"Science"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/ng2116","article-title":"Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans.","volume":"39","author":"A Keinan","year":"2007","journal-title":"Nat Genet"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ng.303","article-title":"Accelerated genetic drift on chromosome X during the human dispersal out of Africa.","volume":"41","author":"A Keinan","year":"2009","journal-title":"Nat Genet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1534\/genetics.104.030171","article-title":"Maximum-likelihood estimation of demographic parameters using the frequency spectrum of unlinked single-nucleotide polymorphisms.","volume":"168","author":"AM Adams","year":"2004","journal-title":"Genetics"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1534\/genetics.166.1.351","article-title":"The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations.","volume":"166","author":"GT Marth","year":"2004","journal-title":"Genetics"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature09298","article-title":"Integrating common and rare genetic variation in diverse human populations.","volume":"467","author":"DM Altshuler","year":"2010","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nature06258","article-title":"A second generation human haplotype map of over 3.1 million SNPs.","volume":"449","author":"KA Frazer","year":"2007","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1101\/gr.4107905","article-title":"Ascertainment bias in studies of human genome-wide polymorphism.","volume":"15","author":"AG Clark","year":"2005","journal-title":"Genome Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1093\/molbev\/msq148","article-title":"Ascertainment biases in SNP chips affect measures of population divergence.","volume":"27","author":"A Albrechtsen","year":"2010","journal-title":"Mol Biol Evol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"e1000477","DOI":"10.1371\/journal.pgen.1000477","article-title":"Designing genome-wide association studies: sample size, power, imputation, and the choice of genotyping chip.","volume":"5","author":"CCa Spencer","year":"2009","journal-title":"PLoS Genet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"e1001337","DOI":"10.1371\/journal.pgen.1001337","article-title":"Quantifying the underestimation of relative risks from genome-wide association studies.","volume":"7","author":"C Spencer","year":"2011","journal-title":"PLoS Genet"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"15942","DOI":"10.1073\/pnas.0507611102","article-title":"Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa.","volume":"102","author":"S Ramachandran","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e1001008","DOI":"10.1371\/journal.pbio.1001008","article-title":"The Importance of Synthetic Associations Will Only Be Resolved Empirically.","volume":"9","author":"DB Goldstein","year":"2011","journal-title":"PLoS Biol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1086\/521987","article-title":"Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering.","volume":"81","author":"SR Browning","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses.","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1117196","article-title":"A fine-scale map of recombination rates and hotspots across the human genome.","volume":"310","author":"S Myers","year":"2005","journal-title":"Science"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T18:55:35Z","timestamp":1539975335000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002600"}},"subtitle":[],"editor":[{"given":"Itsik","family":"Pe'er","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2012,7,5]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002600","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,5]]}}}