{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T18:43:30Z","timestamp":1776537810699,"version":"3.51.2"},"reference-count":127,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T00:00:00Z","timestamp":1290038400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Rev Genet"],"published-print":{"date-parts":[[2010,12]]},"DOI":"10.1038\/nrg2897","type":"journal-article","created":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T12:34:20Z","timestamp":1290083660000},"page":"855-866","source":"Crossref","is-referenced-by-count":1119,"title":["Phenomics: the next challenge"],"prefix":"10.1038","volume":"11","author":[{"given":"David","family":"Houle","sequence":"first","affiliation":[]},{"given":"Diddahally R.","family":"Govindaraju","sequence":"additional","affiliation":[]},{"given":"Stig","family":"Omholt","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,11,18]]},"reference":[{"key":"BFnrg2897_CR1","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1126\/science.3715466","volume":"232","author":"R Lewin","year":"1986","unstructured":"Lewin, R. Proposal to sequence the human genome stirs debate. Science 232, 1598\u20131600 (1986).","journal-title":"Science"},{"key":"BFnrg2897_CR2","unstructured":"Angier, N. Great 15-year project to decipher genes stirs opposition. New York Times (5 Jun 1990)."},{"key":"BFnrg2897_CR3","doi-asserted-by":"publisher","first-page":"S103","DOI":"10.1164\/ajrccm.156.4.12-tac-5","volume":"156","author":"NJ Schork","year":"1997","unstructured":"Schork, N. J. Genetics of complex disease \u2014 approaches, problems, and solutions. Am. J. Respir. Crit. Care Med. 156, S103\u2013S109 (1997). This was perhaps the earliest call for phenomics.","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFnrg2897_CR4","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1021\/bp9900357","volume":"15","author":"CH Schilling","year":"1999","unstructured":"Schilling, C. H., Edwards, J. S. & Palsson, B. O. Toward metabolic phenomics: analysis of genomic data using flux balances. Biotechnol. Prog. 15, 288\u2013295 (1999).","journal-title":"Biotechnol. Prog."},{"key":"BFnrg2897_CR5","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/B978-012730055-9\/50015-X","volume-title":"The Character Concept in Evolutionary Biology","author":"D Houle","year":"2001","unstructured":"Houle, D. in The Character Concept in Evolutionary Biology (ed. Wagner, G.) 109\u2013140 (Academic Press, 2001)."},{"key":"BFnrg2897_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.neuroscience.2009.01.027","volume":"164","author":"RM Bilder","year":"2009","unstructured":"Bilder, R. M. et al. Phenomics: the systematic study of phenotypes on a genome-wide scale. Neuroscience 164, 30\u201342 (2009). An exceptionally well-reasoned justification for phenomic analyses.","journal-title":"Neuroscience"},{"key":"BFnrg2897_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/ng0503-15","volume":"34","author":"N Freimer","year":"2003","unstructured":"Freimer, N. & Sabatti, C. The human phenome project. Nature Genet. 34, 15\u201321 (2003).","journal-title":"Nature Genet."},{"key":"BFnrg2897_CR8","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1114\/1.1313771","volume":"28","author":"JB Bassingthwaighte","year":"2000","unstructured":"Bassingthwaighte, J. B. Strategies for the physiome project. Ann. Biomed. Eng. 28, 1043\u20131058 (2000).","journal-title":"Ann. Biomed. Eng."},{"key":"BFnrg2897_CR9","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/j.1558-5646.1967.tb03413.x","volume":"21","author":"M Soul\u00e9","year":"1967","unstructured":"Soul\u00e9, M. Phenetics of natural populations I. Phenetic relationships of insular populations of the side-blotched lizard. Evolution 21, 584\u2013591 (1967).","journal-title":"Evolution"},{"key":"BFnrg2897_CR10","doi-asserted-by":"publisher","DOI":"10.1037\/13474-000","volume-title":"Hereditary Genius","author":"F Galton","year":"1869","unstructured":"Galton, F. Hereditary Genius (Macmillan and Co., London, 1869)."},{"key":"BFnrg2897_CR11","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1017\/S0080456800012163","volume":"52","author":"R Fisher","year":"1918","unstructured":"Fisher, R. The correlation between relatives on the supposition of Mendelian inheritance. Trans. R. Soc. Edinb. Earth Sci. 52, 399\u2013433 (1918).","journal-title":"Trans. R. Soc. Edinb. Earth Sci."},{"key":"BFnrg2897_CR12","volume-title":"On the Mode of Communication of Cholera","author":"J Snow","year":"1860","unstructured":"Snow, J. On the Mode of Communication of Cholera. (John Churchill, London, 1860)."},{"key":"BFnrg2897_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1098\/rsta.1903.0001","volume":"200","author":"K Pearson","year":"1903","unstructured":"Pearson, K. Mathematical contributions to the theory of evolution. XI. On the influence of natural selection on the variability and correlation of organs. Philos. Trans. R. Soc. Lond. A 200, 1\u201366 (1903).","journal-title":"Philos. Trans. R. Soc. Lond. A"},{"key":"BFnrg2897_CR14","first-page":"557","volume":"20","author":"S Wright","year":"1921","unstructured":"Wright, S. Correlation and causation. J. Agric. Res. 20, 557\u2013585 (1921).","journal-title":"J. Agric. Res."},{"key":"BFnrg2897_CR15","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S0168-9525(01)02310-1","volume":"17","author":"RC Jansen","year":"2001","unstructured":"Jansen, R. C. & Nap, J. P. Genetical genomics: the added value from segregation. Trends Genet. 17, 388\u2013391 (2001).","journal-title":"Trends Genet."},{"key":"BFnrg2897_CR16","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/nrg996","volume":"4","author":"RC Jansen","year":"2003","unstructured":"Jansen, R. C. Studying complex biological systems using multifactorial perturbation. Nature Rev. Genet. 4, 145\u2013151 (2003).","journal-title":"Nature Rev. Genet."},{"key":"BFnrg2897_CR17","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/nature07633","volume":"456","author":"MV Rockman","year":"2008","unstructured":"Rockman, M. V. Reverse engineering the genotype\u2013phenotype map with natural genetic variation. Nature 456, 738\u2013744 (2008). A stimulating review of how to find links between parts of the genotype\u2013phenotype map.","journal-title":"Nature"},{"key":"BFnrg2897_CR18","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature06756","volume":"452","author":"GP Wagner","year":"2008","unstructured":"Wagner, G. P. et al. Pleiotropic scaling of gene effects and the 'cost of complexity'. Nature 452, 470\u2013472 (2008).","journal-title":"Nature"},{"key":"BFnrg2897_CR19","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1534\/genetics.106.060269","volume":"173","author":"XL He","year":"2006","unstructured":"He, X. L. & Zhang, J. Z. Toward a molecular understanding of pleiotropy. Genetics 173, 1885\u20131891 (2006).","journal-title":"Genetics"},{"key":"BFnrg2897_CR20","doi-asserted-by":"publisher","first-page":"18034","DOI":"10.1073\/pnas.1004666107","volume":"107","author":"Z Wang","year":"2010","unstructured":"Wang, Z., Liao, B. & Zhang, J. Genomic patterns of pleiotropy and the evolution of complexity. Proc. Natl Acad. Sci. USA 107, 18034\u201318039 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrg2897_CR21","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/BF01067774","volume":"10","author":"MB Sokolowski","year":"1980","unstructured":"Sokolowski, M. B. Foraging strategies of Drosophila melanogaster: a chromosomal analysis. Behav. Genet. 10, 291\u2013302 (1980).","journal-title":"Behav. Genet."},{"key":"BFnrg2897_CR22","doi-asserted-by":"publisher","first-page":"e1000609","DOI":"10.1371\/journal.pgen.1000609","volume":"5","author":"CF Kent","year":"2009","unstructured":"Kent, C. F., Daskalchuk, T., Cook, L., Sokolowski, M. B. & Greenspan, R. J. The Drosophila foraging gene mediates adult plasticity and gene\u2013environment interactions in behaviour, metabolites, and gene expression in response to food deprivation. PLoS Genet. 5, e1000609 (2009).","journal-title":"PLoS Genet."},{"key":"BFnrg2897_CR23","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/nature09410","volume":"467","author":"H Lango Allen","year":"2010","unstructured":"Lango Allen, H. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832\u2013838 (2010).","journal-title":"Nature"},{"key":"BFnrg2897_CR24","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nature08494","volume":"461","author":"TA Manolio","year":"2009","unstructured":"Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747\u2013753 (2009).","journal-title":"Nature"},{"key":"BFnrg2897_CR25","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/ng.610","volume":"42","author":"J Park","year":"2010","unstructured":"Park, J. et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nature Genet. 42, 570\u2013575 (2010).","journal-title":"Nature Genet."},{"key":"BFnrg2897_CR26","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/nature09270","volume":"466","author":"TM Teslovich","year":"2010","unstructured":"Teslovich, T. M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707\u2013713 (2010).","journal-title":"Nature"},{"key":"BFnrg2897_CR27","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/456018a","volume":"456","author":"B Maher","year":"2008","unstructured":"Maher, B. Personal genomes: the case of the missing heritability. Nature 456, 18\u201321 (2008).","journal-title":"Nature"},{"key":"BFnrg2897_CR28","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/ng.608","volume":"42","author":"J Yang","year":"2010","unstructured":"Yang, J. et al. Common SNPs explain a large proportion of the heritability for human height. Nature Genet. 42, 565\u2013569 (2010). This study shows that the appearance of 'missing heritability' is created by stringent statistical testing of individual associations and that known SNPs can explain almost all of the variation in human height.","journal-title":"Nature Genet."},{"key":"BFnrg2897_CR29","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1056\/NEJMp0806284","volume":"360","author":"DB Goldstein","year":"2009","unstructured":"Goldstein, D. B. Common genetic variation and human traits. N. Engl. J. Med. 360, 1696\u20131698 (2009).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg2897_CR30","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/genetics\/49.4.725","volume":"49","author":"M Kimura","year":"1964","unstructured":"Kimura, M. & Crow, J. F. The number of alleles that can be maintained in a finite population. Genetics 49, 725\u2013738 (1964).","journal-title":"Genetics"},{"key":"BFnrg2897_CR31","volume-title":"The Mathematical Theory of Quantitative Genetics","author":"MG Bulmer","year":"1980","unstructured":"Bulmer, M. G. The Mathematical Theory of Quantitative Genetics. (Oxford Univ. Press, 1980)."},{"key":"BFnrg2897_CR32","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1098\/rstb.2009.0203","volume":"365","author":"WG Hill","year":"2010","unstructured":"Hill, W. G. Understanding and using quantitative genetic variation. Philos. Trans. R. Soc. B 365, 73\u201385 (2010).","journal-title":"Philos. Trans. R. Soc. B"},{"key":"BFnrg2897_CR33","doi-asserted-by":"publisher","first-page":"184","DOI":"10.3945\/ajcn.2009.28403","volume":"91","author":"SX Li","year":"2010","unstructured":"Li, S. X. et al. Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. American Journal of Clinical Nutrition 91, 184\u2013190 (2010).","journal-title":"American Journal of Clinical Nutrition"},{"key":"BFnrg2897_CR34","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.2337\/db08-0504","volume":"57","author":"H Lango","year":"2008","unstructured":"Lango, H. et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57, 3129\u20133135 (2008).","journal-title":"Diabetes"},{"key":"BFnrg2897_CR35","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1056\/NEJMoa0804742","volume":"359","author":"JB Meigs","year":"2008","unstructured":"Meigs, J. B. et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N. Engl. J. Med. 359, 2208\u20132219 (2008).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg2897_CR36","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1056\/NEJMoa0907727","volume":"362","author":"S Wacholder","year":"2010","unstructured":"Wacholder, S. et al. Performance of common genetic variants in breast-cancer risk models. N. Engl. J. Med. 362, 986\u2013993 (2010).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg2897_CR37","doi-asserted-by":"publisher","first-page":"b4838","DOI":"10.1136\/bmj.b4838","volume":"340","author":"PJ Talmud","year":"2010","unstructured":"Talmud, P. J. et al. Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. BMJ 340, b4838 (2010).","journal-title":"BMJ"},{"key":"BFnrg2897_CR38","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1007\/s00125-009-1362-3","volume":"52","author":"T Spars\u00f8","year":"2009","unstructured":"Spars\u00f8, T. et al. Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene\u2013gene interaction. Diabetologia 52, 1308\u20131314 (2009).","journal-title":"Diabetologia"},{"key":"BFnrg2897_CR39","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1093\/ije\/dyl001","volume":"35","author":"AV Buchanan","year":"2006","unstructured":"Buchanan, A. V., Weiss, K. M. & Fullerton, S. M. Dissecting complex disease: the quest for the philosopher's stone? Int. J. Epidemiol. 35, 562\u2013571 (2006).","journal-title":"Int. J. Epidemiol."},{"key":"BFnrg2897_CR40","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1111\/j.1420-9101.2010.02021.x","volume":"23","author":"LJ Robson","year":"2010","unstructured":"Robson, L. J. & Gwynne, D. T. Measuring sexual selection on females in sex-role-reversed Mormon crickets (Anabrus simplex, Orthoptera: Tettigoniidae). J. Evol. Biol. 23, 1528\u20131537 (2010).","journal-title":"J. Evol. Biol."},{"key":"BFnrg2897_CR41","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/j.1558-5646.1983.tb00236.x","volume":"37","author":"R Lande","year":"1983","unstructured":"Lande, R. & Arnold, S. J. The measurement of selection on correlated characters. Evolution 37, 1210\u20131226 (1983).","journal-title":"Evolution"},{"key":"BFnrg2897_CR42","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1073\/pnas.0906195106","volume":"107","author":"D Houle","year":"2010","unstructured":"Houle, D. Numbering the hairs on our heads: the shared challenge and promise of phenomics. Proc. Natl Acad. Sci. USA 107, 1793\u20131799 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrg2897_CR43","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1038\/nrg2670","volume":"10","author":"R Plomin","year":"2009","unstructured":"Plomin, R., Haworth, C. M. A. & Davis, O. S. P. Common disorders are quantitative traits. Nature Rev. Genet. 10, 872\u2013878 (2009).","journal-title":"Nature Rev. Genet."},{"key":"BFnrg2897_CR44","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1176\/appi.ajp.160.4.636","volume":"160","author":"I Gottesman","year":"2003","unstructured":"Gottesman, I. & Gould, T. D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160, 636\u2013645 (2003). An insightful review on the utility of intermediate phenotypes or biomarkers to predict psychiatric disorders.","journal-title":"Am. J. Psychiatry"},{"key":"BFnrg2897_CR45","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1023\/A:1013323318612","volume":"112\u2013113","author":"JG Kingsolver","year":"2001","unstructured":"Kingsolver, J. G., Gomulkiewicz, R. & Carter, P. A. Variation, selection and evolution of function-valued traits. Genetica 112\u2013113, 87\u2013104 (2001). A review of a powerful approach to studying the class of phenotypes that are continuous functions of time or position.","journal-title":"Genetica"},{"key":"BFnrg2897_CR46","volume-title":"Multivariate Analysis of Quality: An Introduction","author":"H Martens","year":"2001","unstructured":"Martens, H. & Martens, M. Multivariate Analysis of Quality: An Introduction. (J. Wiley and Sons, Chichester, UK, 2001)."},{"key":"BFnrg2897_CR47","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","volume":"58","author":"R Tibshirani","year":"1996","unstructured":"Tibshirani, R. Regression shrinkage and selection via the Lasso. J. R. Stat. Soc. Ser. B 58, 267\u2013288 (1996).","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"BFnrg2897_CR48","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1111\/j.0014-3820.2005.tb01041.x","volume":"59","author":"JG Mezey","year":"2005","unstructured":"Mezey, J. G. & Houle, D. The dimensionality of genetic variation for wing shape in Drosophila melanogaster. Evolution 59, 1027\u20131038 (2005).","journal-title":"Evolution"},{"key":"BFnrg2897_CR49","doi-asserted-by":"publisher","first-page":"3938","DOI":"10.3168\/jds.S0022-0302(04)73533-X","volume":"87","author":"A Sewalem","year":"2004","unstructured":"Sewalem, A., Kistemaker, G. J., Miglior, F. & Van Doormaal, B. J. Analysis of the relationship between type traits and functional survival in Canadian Holsteins using a Weibull proportional hazards model. J. Dairy Sci. 87, 3938\u20133946 (2004).","journal-title":"J. Dairy Sci."},{"key":"BFnrg2897_CR50","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/bib\/bbp044","volume":"11","author":"MF Ochs","year":"2010","unstructured":"Ochs, M. F. Knowledge-based data analysis comes of age. Brief. Bioinformatics 11, 30\u201339 (2010).","journal-title":"Brief. Bioinformatics"},{"key":"BFnrg2897_CR51","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1159\/000078209","volume":"105","author":"J Zhu","year":"2004","unstructured":"Zhu, J. et al. An integrative genomics approach to the reconstruction of gene networks in segregating populations. Cytogenet. Genome Res. 105, 363\u2013374 (2004).","journal-title":"Cytogenet. Genome Res."},{"key":"BFnrg2897_CR52","first-page":"1046","volume":"2","author":"RH Li","year":"2006","unstructured":"Li, R. H. et al. Structural model analysis of multiple quantitative traits. PLoS Genet. 2, 1046\u20131057 (2006).","journal-title":"PLoS Genet."},{"key":"BFnrg2897_CR53","volume-title":"Model Selection and Multi-model Inference: A Practical Information-Theoretic Approach","author":"KP Burnham","year":"2002","unstructured":"Burnham, K. P. & Anderson, D. R. Model Selection and Multi-model Inference: A Practical Information-Theoretic Approach. (Springer, New York, 2002)."},{"key":"BFnrg2897_CR54","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1198\/016214503000000819","volume":"98","author":"G Claeskens","year":"2003","unstructured":"Claeskens, G. & Hjort, N. L. The focused information criterion. J. Am. Stat. Assoc. 98, 900\u2013916 (2003).","journal-title":"J. Am. Stat. Assoc."},{"key":"BFnrg2897_CR55","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1007\/BFb0062108","volume":"973","author":"S Wold","year":"1983","unstructured":"Wold, S., Martens, H. & Wold, H. The multivariate calibration-problem in chemistry solved by the PLS method. Lect. Notes Math. 973, 286\u2013293 (1983).","journal-title":"Lect. Notes Math."},{"key":"BFnrg2897_CR56","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/gepi.20041","volume":"28","author":"A Bureau","year":"2005","unstructured":"Bureau, A. et al. Identifying SNPs predictive of phenotype using random forests. Genet. Epidemiol. 28, 171\u2013182 (2005). The introduction of a powerful non-parametric technique to QTL mapping.","journal-title":"Genet. Epidemiol."},{"key":"BFnrg2897_CR57","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1214\/ss\/1009213726","volume":"16","author":"L Breiman","year":"2001","unstructured":"Breiman, L. Statistical modeling: the two cultures. Stat. Sci. 16, 199\u2013215 (2001). A clear introduction to several powerful techniques for the statistical modelling of high-dimensional data.","journal-title":"Stat. Sci."},{"key":"BFnrg2897_CR58","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1098\/rstb.2009.0203","volume":"365","author":"WG Hill","year":"2010","unstructured":"Hill, W. G. Understanding and using quantitative genetic variation. Philo. Trans. R. Soc. B 365, 73\u201385 (2010).","journal-title":"Philo. Trans. R. Soc. B"},{"key":"BFnrg2897_CR59","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1534\/genetics.108.087064","volume":"179","author":"H Rajasingh","year":"2008","unstructured":"Rajasingh, H., Gjuvsland, A. B., Vage, D. I. & Omholt, S. W. When parameters in dynamic models become phenotypes: a case study on flesh pigmentation in the Chinook salmon (Oncorhynchus tshawytscha). Genetics 179, 1113\u20131118 (2008).","journal-title":"Genetics"},{"key":"BFnrg2897_CR60","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nrm1054","volume":"4","author":"PJ Hunter","year":"2003","unstructured":"Hunter, P. J. & Borg, T. K. Integration from proteins to organs: the Physiome Project. Nature Rev. Mol. Cell Biol. 4, 237\u2013243 (2003).","journal-title":"Nature Rev. Mol. Cell Biol."},{"key":"BFnrg2897_CR61","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/genetics\/155.2.969","volume":"155","author":"SW Omholt","year":"2000","unstructured":"Omholt, S. W., Plahte, E., Oyehaug, L. & Xiang, K. Gene regulatory networks generating the phenomena of additivity, dominance and epistasis. Genetics 155, 969\u2013980 (2000).","journal-title":"Genetics"},{"key":"BFnrg2897_CR62","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1752-0509-1-32","volume":"1","author":"AB Gjuvsland","year":"2007","unstructured":"Gjuvsland, A. B., Hayes, B. J., Meuwissen, T. H., Plahte, E. & Omholt, S. W. Nonlinear regulation enhances the phenotypic expression of trans-acting genetic polymorphisms. BMC Syst. Biol. 1, 32 (2007).","journal-title":"BMC Syst. Biol."},{"key":"BFnrg2897_CR63","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1752-0509-1-57","volume":"1","author":"AB Gjuvsland","year":"2007","unstructured":"Gjuvsland, A. B., Plahte, E. & Omholt, S. W. Threshold-dominated regulation hides genetic variation in gene expression networks. BMC Syst. Biol. 1, 57 (2007).","journal-title":"BMC Syst. Biol."},{"key":"BFnrg2897_CR64","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1534\/genetics.166.4.1715","volume":"166","author":"J Peccoud","year":"2004","unstructured":"Peccoud, J. et al. The selective values of alleles in a molecular network model are context dependent. Genetics 166, 1715\u20131725 (2004).","journal-title":"Genetics"},{"key":"BFnrg2897_CR65","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1071\/AR05155","volume":"56","author":"SM Welch","year":"2005","unstructured":"Welch, S. M., Dong, Z., Roe, J. L. & Das, S. Flowering time control: gene network modelling and the link to quantitative genetics. Aust. J. Agric. Res. 56, 919\u2013936 (2005).","journal-title":"Aust. J. Agric. Res."},{"key":"BFnrg2897_CR66","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.pbi.2009.01.006","volume":"12","author":"M Cooper","year":"2009","unstructured":"Cooper, M., van Eeuwijk, F. A., Hammer, G. L., Podlich, D. W. & Messina, C. Modeling QTL for complex traits: detection and context for plant breeding. Curr. Opin. Plant Biol. 12, 231\u2013240 (2009).","journal-title":"Curr. Opin. Plant Biol."},{"key":"BFnrg2897_CR67","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1071\/AR05154","volume":"56","author":"M Cooper","year":"2005","unstructured":"Cooper, M., Podlich, D. W. & Smith, O. S. Gene-to-phenotype models and complex trait genetics. Aust. J. Agric. Res. 56, 895\u2013918 (2005).","journal-title":"Aust. J. Agric. Res."},{"key":"BFnrg2897_CR68","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nature08838","volume":"464","author":"I Salazar-Ciudad","year":"2010","unstructured":"Salazar-Ciudad, I. & Jernvall, J. A computational model of teeth and the developmental origins of morphological variation. Nature 464, 583\u2013586 (2010). A developmental model that produces three-dimensional predictions of tooth morphology and can mimic the variation observed in seal teeth.","journal-title":"Nature"},{"key":"BFnrg2897_CR69","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1534\/genetics.106.058859","volume":"175","author":"AB Gjuvsland","year":"2006","unstructured":"Gjuvsland, A. B., Hayes, B. J., Omholt, S. W. & Carlborg, O. Statistical epistasis is a generic feature of gene regulatory networks. Genetics 175, 411\u2013420 (2006).","journal-title":"Genetics"},{"key":"BFnrg2897_CR70","doi-asserted-by":"publisher","first-page":"e9379","DOI":"10.1371\/journal.pone.0009379","volume":"5","author":"AB Gjuvsland","year":"2010","unstructured":"Gjuvsland, A. B., Plahte, E., \u00c5dn\u00f8y, T. & Omholt, S. W. Allele interaction \u2014 single locus genetics meets regulatory biology. PLoS ONE 5, e9379 (2010).","journal-title":"PLoS ONE"},{"key":"BFnrg2897_CR71","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1098\/rsta.2010.0048","volume":"368","author":"P Hunter","year":"2010","unstructured":"Hunter, P. et al. A vision and strategy for the virtual physiological human in 2010 and beyond. Philos. Trans. R. Soc. A 368, 2595\u20132614 (2010).","journal-title":"Philos. Trans. R. Soc. A"},{"key":"BFnrg2897_CR72","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1109\/RBME.2009.2036204","volume":"2","author":"PJ Hunter","year":"2009","unstructured":"Hunter, P. J. & Viceconti, M. The VPH\u2013Physiome Project: standards and tools for multiscale modeling in clinical applications. IEEE Rev. Biomed. Eng. 2, 40\u201353 (2009).","journal-title":"IEEE Rev. Biomed. Eng."},{"key":"BFnrg2897_CR73","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1023\/A:1011084330767","volume":"61","author":"M Nash","year":"2000","unstructured":"Nash, M. & Hunter, P. Computational mechanics of the heart. J. Elast. 61, 113\u2013141 (2000).","journal-title":"J. Elast."},{"key":"BFnrg2897_CR74","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1182\/blood-2008-04-153239","volume":"113","author":"BJ Wouters","year":"2009","unstructured":"Wouters, B. J., Lowenberg, B. & Delwel, R. A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects. Blood 113, 291\u2013298 (2009).","journal-title":"Blood"},{"key":"BFnrg2897_CR75","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1126\/science.286.5439.531","volume":"286","author":"TR Golub","year":"1999","unstructured":"Golub, T. R. et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531\u2013537 (1999).","journal-title":"Science"},{"key":"BFnrg2897_CR76","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev.arplant.043008.092114","volume":"60","author":"D Kliebenstein","year":"2009","unstructured":"Kliebenstein, D. Quantitative genomics: analyzing intraspecific variation using global gene expression polymorphisms or eQTLs. Annu. Rev. Plant Biol. 60, 93\u2013114 (2009).","journal-title":"Annu. Rev. Plant Biol."},{"key":"BFnrg2897_CR77","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/bioinformatics\/btg011","volume":"19","author":"TJ Chu","year":"2003","unstructured":"Chu, T. J., Glymour, C., Scheines, R. & Spirtes, P. A statistical problem for inference to regulatory structure from associations of gene expression measurements with microarrays. Bioinformatics 19, 1147\u20131152 (2003).","journal-title":"Bioinformatics"},{"key":"BFnrg2897_CR78","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ymeth.2009.12.011","volume":"51","author":"R Sindelka","year":"2010","unstructured":"Sindelka, R., Sidova, M., Svec, D. & Kubista, M. Spatial expression profiles in the Xenopus laevis oocytes measured with qPCR tomography. Methods 51, 87\u201391 (2010).","journal-title":"Methods"},{"key":"BFnrg2897_CR79","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/nature07341","volume":"455","author":"LMF de Godoy","year":"2008","unstructured":"de Godoy, L. M. F. et al. Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 455, 1251\u20131254 (2008).","journal-title":"Nature"},{"key":"BFnrg2897_CR80","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nrm2900","volume":"11","author":"C Choudhary","year":"2010","unstructured":"Choudhary, C. & Mann, M. Decoding signalling networks by mass spectrometry-based proteomics. Nature Rev. Mol. Cell Biol. 11, 427\u2013439 (2010).","journal-title":"Nature Rev. Mol. Cell Biol."},{"key":"BFnrg2897_CR81","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/pcp\/pcn183","volume":"50","author":"Y Sawada","year":"2009","unstructured":"Sawada, Y. et al. Widely targeted metabolomics based on large-scale MS\/MS data for elucidating metabolite accumulation patterns in plants. Plant Cell Physiol. 50, 37\u201347 (2009).","journal-title":"Plant Cell Physiol."},{"key":"BFnrg2897_CR82","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1161\/CIRCGENETICS.108.808329","volume":"1","author":"M Mayr","year":"2008","unstructured":"Mayr, M. Metabolomics ready for the prime time? Circ. Cardiovasc. Genet. 1, 58\u201365 (2008).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"BFnrg2897_CR83","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature06882","volume":"453","author":"E Holmes","year":"2008","unstructured":"Holmes, E. et al. Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453, 396\u2013400 (2008).","journal-title":"Nature"},{"key":"BFnrg2897_CR84","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1161\/CIRCGENETICS.109.852814","volume":"3","author":"SH Shah","year":"2010","unstructured":"Shah, S. H. et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ. Cardiovasc. Genet. 3, 207\u2013214 (2010).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"BFnrg2897_CR85","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nmeth0610-479a","volume":"7","author":"T Walter","year":"2010","unstructured":"Walter, T. et al. Visualization of image data from cells to organisms. Nature Methods 7, 479\u2013479 (2010).","journal-title":"Nature Methods"},{"key":"BFnrg2897_CR86","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.tplants.2007.08.006","volume":"12","author":"JM Montes","year":"2007","unstructured":"Montes, J. M., Melchinger, A. E. & Reif, J. C. Novel throughput phenotyping platforms in plant genetic studies. Trends Plant Sci. 12, 433\u2013436 (2007).","journal-title":"Trends Plant Sci."},{"key":"BFnrg2897_CR87","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1071\/FP09184","volume":"36","author":"KA Nagel","year":"2009","unstructured":"Nagel, K. A. et al. Temperature responses of roots: impact on growth, root system architecture and implications for phenotyping. Funct. Plant Biol. 36, 947\u2013959 (2009).","journal-title":"Funct. Plant Biol."},{"key":"BFnrg2897_CR88","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1152\/jn.00879.2005","volume":"95","author":"AL Vyssotski","year":"2006","unstructured":"Vyssotski, A. L. et al. Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording. J. Neurophysiol. 95, 1263\u20131273 (2006).","journal-title":"J. Neurophysiol."},{"key":"BFnrg2897_CR89","doi-asserted-by":"publisher","first-page":"e8793","DOI":"10.1371\/journal.pone.0008793","volume":"5","author":"JC Simon","year":"2010","unstructured":"Simon, J. C. & Dickinson, M. H. A new chamber for studying the behavior of Drosophila. PLoS ONE 5, e8793 (2010).","journal-title":"PLoS ONE"},{"key":"BFnrg2897_CR90","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1126\/science.1188102","volume":"328","author":"R Rodriguez-Munoz","year":"2010","unstructured":"Rodriguez-Munoz, R., Bretman, A., Slate, J., Walling, C. A. & Tregenza, T. Natural and sexual selection in a wild insect population. Science 328, 1269\u20131272 (2010).","journal-title":"Science"},{"key":"BFnrg2897_CR91","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.chb.2005.05.002","volume":"23","author":"P Carlbring","year":"2007","unstructured":"Carlbring, P. et al. Internet vs. paper and pencil administration of questionnaires commonly used in panic\/agoraphobia research. Comput. Human Behav. 23, 1421\u20131434 (2007).","journal-title":"Comput. Human Behav."},{"key":"BFnrg2897_CR92","doi-asserted-by":"publisher","first-page":"19015","DOI":"10.1073\/pnas.0509436102","volume":"102","author":"Y Ohya","year":"2005","unstructured":"Ohya, Y. et al. High-dimensional and large-scale phenotyping of yeast mutants. Proc. Natl Acad. Sci. USA 102, 19015\u201319020 (2005). This study describes an automated imaging system that measures over 400 morphological parameters of yeast cells.","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrg2897_CR93","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nmeth.1227","volume":"5","author":"KH Chung","year":"2008","unstructured":"Chung, K. H., Crane, M. M. & Lu, H. Automated on-chip rapid microscopy, phenotyping and sorting of C. elegans. Nature Methods 5, 637\u2013643 (2008). This paper describes a system for the rapid, automated manipulation and measurement of nematode worms.","journal-title":"Nature Methods"},{"key":"BFnrg2897_CR94","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-685-6","volume-title":"The Hand Book of Biomarkers","author":"K Jain","year":"2010","unstructured":"Jain, K. The Hand Book of Biomarkers. (Springer, New York, 2010)."},{"key":"BFnrg2897_CR95","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0065-2660(08)00602-0","volume":"62","author":"DR Govindaraju","year":"2008","unstructured":"Govindaraju, D. R. et al. Genetics of the Framingham Heart Study population. Adv. Genet. 62, 33\u201365 (2008).","journal-title":"Adv. Genet."},{"key":"BFnrg2897_CR96","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1056\/NEJMoa055373","volume":"355","author":"TJ Wang","year":"2006","unstructured":"Wang, T. J. et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N. Engl. J. Med. 355, 2631\u20132639 (2006).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg2897_CR97","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/aje\/kwk115","volume":"165","author":"TB Harris","year":"2007","unstructured":"Harris, T. B. et al. Age, Gene\/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am. J. Epidemiol. 165, 1076\u20131087 (2007).","journal-title":"Am. J. Epidemiol."},{"key":"BFnrg2897_CR98","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1161\/CIRCGENETICS.108.829747","volume":"2","author":"BM Psaty","year":"2009","unstructured":"Psaty, B. M. et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ. Cardiovasc. Genet. 2, 73\u201380 (2009).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"BFnrg2897_CR99","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1073\/pnas.0906199106","volume":"107","author":"SG Byars","year":"2010","unstructured":"Byars, S. G., Ewbank, D., Govindaraju, D. R. & Stearns, S. C. Natural selection in a contemporary human population. Proc. Natl Acad. Sci. USA 107, 1787\u20131792 (2010). The first comprehensive review of selection in contemporary human populations.","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrg2897_CR100","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1001\/jama.1993.03510130069033","volume":"270","author":"ML Slattery","year":"1993","unstructured":"Slattery, M. L. & Kerber, R. A. A comprehensive evaluation of family history and breast cancer risk. The Utah Population Database. JAMA 270, 1563\u20131568 (1993).","journal-title":"JAMA"},{"key":"BFnrg2897_CR101","first-page":"131","volume":"17","author":"CG Chute","year":"2010","unstructured":"Chute, C. G., Beck, S. A., Fisk, T. B. & Mohr, D. N. The Enterprise Data Trust at Mayo Clinic: a semantically integrated warehouse of biomedical data. JAMA 17, 131\u2013135 (2010).","journal-title":"JAMA"},{"key":"BFnrg2897_CR102","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1177\/14034948010290040201","volume":"29","author":"J Olsen","year":"2001","unstructured":"Olsen, J. et al. The Danish National Birth Cohort \u2014 its background, structure and aim. Scand. J. Public Health 29, 300\u2013307 (2001).","journal-title":"Scand. J. Public Health"},{"key":"BFnrg2897_CR103","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/ng1007-1181","volume":"39","author":"MD Mailman","year":"2007","unstructured":"Mailman, M. D. et al. The NCBI dbGaP database of genotypes and phenotypes. Nature Genet. 39, 1181\u20131186 (2007).","journal-title":"Nature Genet."},{"key":"BFnrg2897_CR104","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1039\/b927258e","volume":"10","author":"MM Crane","year":"2010","unstructured":"Crane, M. M., Chung, K., Stirman, J. & Lu, H. Microfluidics-enabled phenotyping, imaging, and screening of multicellular organisms. Lab Chip 10, 1509\u20131517 (2010).","journal-title":"Lab Chip"},{"key":"BFnrg2897_CR105","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/nature08605","volume":"462","author":"DA Giljohann","year":"2009","unstructured":"Giljohann, D. A. & Mirkin, C. A. Drivers of biodiagnostic development. Nature 462, 461\u2013464 (2009).","journal-title":"Nature"},{"key":"BFnrg2897_CR106","doi-asserted-by":"publisher","first-page":"11694","DOI":"10.1073\/pnas.0704820104","volume":"104","author":"A Rzhetsky","year":"2007","unstructured":"Rzhetsky, A., Wajngurt, D., Park, N. & Zheng, T. Probing genetic overlap among complex human phenotypes. Proc. Natl Acad. Sci. USA 104, 11694\u201311699 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrg2897_CR107","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1152\/physiol.00016.2004","volume":"19","author":"RG Pautler","year":"2004","unstructured":"Pautler, R. G. Mouse MRI: concepts and applications in physiology. Physiology 19, 168\u2013175 (2004).","journal-title":"Physiology"},{"key":"BFnrg2897_CR108","doi-asserted-by":"publisher","first-page":"H2979","DOI":"10.1152\/ajpheart.00084.2005","volume":"288","author":"OJ How","year":"2005","unstructured":"How, O. J. et al. Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts. Am. J. Physiol. Heart Circ. Physiol. 288, H2979\u2013H2985 (2005).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnrg2897_CR109","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1152\/japplphysiol.00549.2009","volume":"107","author":"JC Han","year":"2009","unstructured":"Han, J. C. et al. A unique micromechanocalorimeter for simultaneous measurement of heat rate and force production of cardiac trabeculae carneae. J. Appl. Physiol. 107, 946\u2013951 (2009).","journal-title":"J. Appl. Physiol."},{"key":"BFnrg2897_CR110","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1046\/j.1365-2818.1998.00414.x","volume":"192","author":"AA Young","year":"1998","unstructured":"Young, A. A., Legrice, I. J., Young, M. A. & Smaill, B. H. Extended confocal microscopy of myocardial laminae and collagen network. J. Microsc. 192, 139\u2013150 (1998).","journal-title":"J. Microsc."},{"key":"BFnrg2897_CR111","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1161\/01.CIR.0000048892.83521.58","volume":"107","author":"EG Lakatta","year":"2003","unstructured":"Lakatta, E. G. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part I: aging arteries: a 'set up' for vascular disease. Circulation 107, 139\u2013146 (2003).","journal-title":"Circulation"},{"key":"BFnrg2897_CR112","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1161\/01.CIR.0000048893.62841.F7","volume":"107","author":"EG Lakatta","year":"2003","unstructured":"Lakatta, E. G. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part II: the aging heart in health: links to heart disease. Circulation 107, 346\u2013354 (2003).","journal-title":"Circulation"},{"key":"BFnrg2897_CR113","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1161\/01.CIR.0000048894.99865.02","volume":"107","author":"EG Lakatta","year":"2003","unstructured":"Lakatta, E. G. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part III: cellular and molecular clues to heart and arterial aging. Circulation 107, 490\u2013497 (2003).","journal-title":"Circulation"},{"key":"BFnrg2897_CR114","volume-title":"The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans","author":"CE Finch","year":"2007","unstructured":"Finch, C. E. The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans. (Academic Press, 2007)."},{"key":"BFnrg2897_CR115","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/nrg2509","volume":"10","author":"DJ Wilkinson","year":"2009","unstructured":"Wilkinson, D. J. Stochastic modelling for quantitative description of heterogeneous biological systems. Nature Rev. Genet. 10, 122\u2013133 (2009).","journal-title":"Nature Rev. Genet."},{"key":"BFnrg2897_CR116","first-page":"47","volume-title":"Towards a Theoretical Biology","author":"J Burns","year":"1970","unstructured":"Burns, J. in Towards a Theoretical Biology Vol. 3, (ed. Waddington, C. H.) 47\u201351 (Edinburgh Univ. Press, 1970)."},{"key":"BFnrg2897_CR117","volume-title":"The Strategy of the Genes","author":"CH Waddington","year":"1957","unstructured":"Waddington, C. H. The Strategy of the Genes. (Macmillan, New York, 1957)."},{"key":"BFnrg2897_CR118","volume-title":"The Genetic Basis of Evolutionary Change","author":"R Lewontin","year":"1974","unstructured":"Lewontin, R. The Genetic Basis of Evolutionary Change. (Columbia Univ. Press, New York, 1974)."},{"key":"BFnrg2897_CR119","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"G Davey Smith","year":"2003","unstructured":"Davey Smith, G. & Ebrahim, S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32, 1\u201322 (2003).","journal-title":"Int. J. Epidemiol."},{"key":"BFnrg2897_CR120","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1111\/j.1365-2265.2008.03490.x","volume":"70","author":"D Preiss","year":"2009","unstructured":"Preiss, D. & Sattar, N. Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence. Clin. Endocrinol. 70, 815\u2013828 (2009).","journal-title":"Clin. Endocrinol."},{"issue":"18","key":"BFnrg2897_CR121","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1001\/jama.2009.1619","volume":"302","author":"The Emerging Risk Factors Collabora","year":"2009","unstructured":"Emerging Risk Factors Collaboration et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302, 1993\u20132000 (2009).","journal-title":"JAMA"},{"key":"BFnrg2897_CR122","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1126\/science.1064852","volume":"294","author":"LA Pennacchio","year":"2001","unstructured":"Pennacchio, L. A. et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294, 169\u2013173 (2001).","journal-title":"Science"},{"key":"BFnrg2897_CR123","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/ng.75","volume":"40","author":"S Kathiresan","year":"2008","unstructured":"Kathiresan, S. et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nature Genet. 40, 189\u2013197 (2008).","journal-title":"Nature Genet."},{"key":"BFnrg2897_CR124","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1126\/science.3287615","volume":"240","author":"JA Swets","year":"1988","unstructured":"Swets, J. A. Measuring the accuracy of diagnostic systems. Science 240, 1285\u20131293 (1988).","journal-title":"Science"},{"key":"BFnrg2897_CR125","doi-asserted-by":"publisher","first-page":"e1000934","DOI":"10.1371\/journal.pgen.1000934","volume":"6","author":"F Liu","year":"2010","unstructured":"Liu, F. et al. Digital quantification of human eye color highlights genetic association of three new loci. PLoS Genet. 6, e1000934 (2010).","journal-title":"PLoS Genet."},{"key":"BFnrg2897_CR126","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nature08800","volume":"465","author":"S Atwell","year":"2010","unstructured":"Atwell, S. et al. Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature 465, 627\u2013631 (2010).","journal-title":"Nature"},{"key":"BFnrg2897_CR127","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/1471-2164-11-297","volume":"11","author":"P Jumbo-Lucioni","year":"2010","unstructured":"Jumbo-Lucioni, P. et al. Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster. BMC Genomics 11, 297 (2010).","journal-title":"BMC Genomics"}],"container-title":["Nature Reviews Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nrg2897.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrg2897","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrg2897.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T01:56:58Z","timestamp":1740707818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrg2897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,18]]},"references-count":127,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["BFnrg2897"],"URL":"https:\/\/doi.org\/10.1038\/nrg2897","relation":{},"ISSN":["1471-0056","1471-0064"],"issn-type":[{"value":"1471-0056","type":"print"},{"value":"1471-0064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,18]]}}}