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2019 | OriginalPaper | Buchkapitel

12. Exposome-Wide Association Studies: A Data-Driven Approach for Searching for Exposures Associated with Phenotype

verfasst von : Chirag J. Patel

Erschienen in: Unraveling the Exposome

Verlag: Springer International Publishing

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Abstract

The promise of a unified way to measure the human exposome is the discovery of novel environmental factors associated with and potentially causative of disease. The human exposome has been tentatively defined as the totality of environmental exposures such as dietary nutrients, pharmaceutical drugs, infectious agents, and pollutants encountered from birth to death. Much as human genetics has benefited from high-throughput profiling in the form of genome-wide association studies (GWAS), a data-driven paradigm for the exposome is needed to systematically and reproducibly discover the environmental determinants of disease. In this chapter, we describe methods for associating the exposome with phenotypic state such as disease. Specifically, this chapter will describe hands-on analytic examples and data to search the exposome for correlates with phenotype, called the “environment/exposome-wide association study” (EWAS). First, we will describe the philosophy behind such a study, including transparency and mitigation of the chances for selection biases. Second, we will describe how to mitigate chances of type 1 error and investigate the possibility of true signals in a sea of possible false positives. We will describe open-source tools for visualization and display of correlated data to enable investigators to efficiently ascertain patterns in phenotypic associations. We end by describing a few success stories of the approach.

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Literatur
Zurück zum Zitat Bartell SM, Griffith WC, Faustman EM (2004) Temporal error in biomarker-based mean exposure estimates for individuals. J Expo Anal Environ Epidemiol 14:173–179CrossRef Bartell SM, Griffith WC, Faustman EM (2004) Temporal error in biomarker-based mean exposure estimates for individuals. J Expo Anal Environ Epidemiol 14:173–179CrossRef
Zurück zum Zitat Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodology 57(1):289–300 Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodology 57(1):289–300
Zurück zum Zitat Butte AJ, Kohane IS (2000) Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements. Pac Symp Biocomput 5:418–429 Butte AJ, Kohane IS (2000) Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements. Pac Symp Biocomput 5:418–429
Zurück zum Zitat Centers for Disease Control and Prevention (CDC), and National Center for Health Statistics (NCHS) (2013a) National Health and Nutrition Examination Survey Data, 1999–2000. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville http://www.cdc.gov/nchs/nhanes/nhanes99_00.htm Centers for Disease Control and Prevention (CDC), and National Center for Health Statistics (NCHS) (2013a) National Health and Nutrition Examination Survey Data, 1999–2000. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville http://​www.​cdc.​gov/​nchs/​nhanes/​nhanes99_​00.​htm
Zurück zum Zitat Centers for Disease Control and Prevention (CDC), and National Center for Health Statistics (NCHS) (2013b) National Health and Nutrition Examination Survey Data, 2001–2002. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville http://www.cdc.gov/nchs/nhanes/nhanes01-02.htm Centers for Disease Control and Prevention (CDC), and National Center for Health Statistics (NCHS) (2013b) National Health and Nutrition Examination Survey Data, 2001–2002. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville http://​www.​cdc.​gov/​nchs/​nhanes/​nhanes01-02.​htm
Zurück zum Zitat Davey Smith G, Ebrahim S (2005) What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 330(7499):1076–1079CrossRef Davey Smith G, Ebrahim S (2005) What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 330(7499):1076–1079CrossRef
Zurück zum Zitat Dennis KK, Marder E, Balshaw DM, Cui Y, Lynes MA, Patti GJ, Rappaport SM, Shaughnessy DT, Vrijheid M, Barr DB (2017) Biomonitoring in the era of the exposome. Environ Health Perspect 125(4):502CrossRef Dennis KK, Marder E, Balshaw DM, Cui Y, Lynes MA, Patti GJ, Rappaport SM, Shaughnessy DT, Vrijheid M, Barr DB (2017) Biomonitoring in the era of the exposome. Environ Health Perspect 125(4):502CrossRef
Zurück zum Zitat Efron B (2010) Large-scale inference. Cambridge University Press, CambridgeCrossRef Efron B (2010) Large-scale inference. Cambridge University Press, CambridgeCrossRef
Zurück zum Zitat Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95(25):14863–14868CrossRef Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95(25):14863–14868CrossRef
Zurück zum Zitat Frayling T, Timpson N, Weedon M, Zeggini E, Freathy R, Lindgren C, Perry J et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894CrossRef Frayling T, Timpson N, Weedon M, Zeggini E, Freathy R, Lindgren C, Perry J et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894CrossRef
Zurück zum Zitat Gibson G (2008) The environmental contribution to gene expression profiles. Nat Rev Genet 9(8):575–581CrossRef Gibson G (2008) The environmental contribution to gene expression profiles. Nat Rev Genet 9(8):575–581CrossRef
Zurück zum Zitat Goldstein D (2009) Common genetic variation and human traits. N Engl J Med 360(17):1696–1698CrossRef Goldstein D (2009) Common genetic variation and human traits. N Engl J Med 360(17):1696–1698CrossRef
Zurück zum Zitat Greenland S, Morgenstern H (2011) Confounding in health research. Annu Rev Public Health 22:189–212CrossRef Greenland S, Morgenstern H (2011) Confounding in health research. Annu Rev Public Health 22:189–212CrossRef
Zurück zum Zitat Hardy J, Singleton A (2009) Genomewide association studies and human disease. N Engl J Med 360(17):1759–1768CrossRef Hardy J, Singleton A (2009) Genomewide association studies and human disease. N Engl J Med 360(17):1759–1768CrossRef
Zurück zum Zitat Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106:9362–9367CrossRef Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106:9362–9367CrossRef
Zurück zum Zitat Hooper L, Ness AR, Smith GD (2001) Antioxidant strategy for cardiovascular diseases. Lancet 357:1705–1706CrossRef Hooper L, Ness AR, Smith GD (2001) Antioxidant strategy for cardiovascular diseases. Lancet 357:1705–1706CrossRef
Zurück zum Zitat International HapMap, Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320CrossRef International HapMap, Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320CrossRef
Zurück zum Zitat Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29(3):306–309CrossRef Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29(3):306–309CrossRef
Zurück zum Zitat Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2(8):e124CrossRef Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2(8):e124CrossRef
Zurück zum Zitat Ioannidis JPA (2016) Exposure-wide epidemiology: revisiting Bradford hill. Stat Med 35(11):1749–1762CrossRef Ioannidis JPA (2016) Exposure-wide epidemiology: revisiting Bradford hill. Stat Med 35(11):1749–1762CrossRef
Zurück zum Zitat Ioannidis JPA, En YL, Poulton R, Chia KS (2009) Researching genetic versus nongenetic determinants of disease: a comparison and proposed unification. Sci Transl Med 1(7):7ps8CrossRef Ioannidis JPA, En YL, Poulton R, Chia KS (2009) Researching genetic versus nongenetic determinants of disease: a comparison and proposed unification. Sci Transl Med 1(7):7ps8CrossRef
Zurück zum Zitat Ioannidis JPA, Tarone R, McLaughlin JK (2011) The false-positive to false-negative ratio in epidemiologic studies. Epidemiology 22(4):450–456CrossRef Ioannidis JPA, Tarone R, McLaughlin JK (2011) The false-positive to false-negative ratio in epidemiologic studies. Epidemiology 22(4):450–456CrossRef
Zurück zum Zitat James G, Witten D, Hastie T, Tibshirani R (2013) An introduction to statistical learning: with applications in R. Springer Texts in Statistics 103. Springer, New YorkCrossRef James G, Witten D, Hastie T, Tibshirani R (2013) An introduction to statistical learning: with applications in R. Springer Texts in Statistics 103. Springer, New YorkCrossRef
Zurück zum Zitat Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA (2009) Circos: an information aesthetic for comparative genomics. Genome Res 19(9):1639–1645CrossRef Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA (2009) Circos: an information aesthetic for comparative genomics. Genome Res 19(9):1639–1645CrossRef
Zurück zum Zitat Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1):559CrossRef Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1):559CrossRef
Zurück zum Zitat Louis B, Germaine M, Sundaram R (2012) Exposome: time for transformative research. Stat Med 31(22):2569–2575CrossRef Louis B, Germaine M, Sundaram R (2012) Exposome: time for transformative research. Stat Med 31(22):2569–2575CrossRef
Zurück zum Zitat Manly BFJ (2007) Randomization, bootstrap and Monte Carlo methods in biology, 3rd edn. Chapman and Hall/CRC, Boca Raton Manly BFJ (2007) Randomization, bootstrap and Monte Carlo methods in biology, 3rd edn. Chapman and Hall/CRC, Boca Raton
Zurück zum Zitat Manolio TA, Brooks LD, Collins FS (2008) A HapMap harvest of insights into the genetics of common disease. J Clin Invest 118(5):1590–1605CrossRef Manolio TA, Brooks LD, Collins FS (2008) A HapMap harvest of insights into the genetics of common disease. J Clin Invest 118(5):1590–1605CrossRef
Zurück zum Zitat Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, Mccarthy MI et al (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753CrossRef Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, Mccarthy MI et al (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753CrossRef
Zurück zum Zitat Manrai AK, Cui Y, Bushel PR, Hall M, Karakitsios S, Mattingly CJ, Ritchie M et al (2017) Informatics and data analytics to support exposome-based discovery for public health. Annu Rev Public Health 38(1):279–294CrossRef Manrai AK, Cui Y, Bushel PR, Hall M, Karakitsios S, Mattingly CJ, Ritchie M et al (2017) Informatics and data analytics to support exposome-based discovery for public health. Annu Rev Public Health 38(1):279–294CrossRef
Zurück zum Zitat McGinnis DP, Brownstein JS, Patel CJ (2016) Environment-wide association study of blood pressure in the national health and nutrition examination survey (1999–2012). Sci Rep 6:30373CrossRef McGinnis DP, Brownstein JS, Patel CJ (2016) Environment-wide association study of blood pressure in the national health and nutrition examination survey (1999–2012). Sci Rep 6:30373CrossRef
Zurück zum Zitat Miller GW, Jones DP (2014) The nature of nurture: refining the definition of the exposome. Toxicol Sci 137(1):1–2CrossRef Miller GW, Jones DP (2014) The nature of nurture: refining the definition of the exposome. Toxicol Sci 137(1):1–2CrossRef
Zurück zum Zitat NCI-NHGRI Working Group on Replication in Association Studies, Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G et al (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660CrossRef NCI-NHGRI Working Group on Replication in Association Studies, Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G et al (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660CrossRef
Zurück zum Zitat Noble WS (2009) How does multiple testing correction work? Nat Biotechnol 27(12):1135–1137CrossRef Noble WS (2009) How does multiple testing correction work? Nat Biotechnol 27(12):1135–1137CrossRef
Zurück zum Zitat Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP et al (1996) Effects of a combination of beta carotene and vitamin a on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155CrossRef Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP et al (1996) Effects of a combination of beta carotene and vitamin a on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155CrossRef
Zurück zum Zitat Patel CJ, Ioannidis JPA (2014a) Studying the elusive environment in large scale. JAMA 311(21):2173–2174CrossRef Patel CJ, Ioannidis JPA (2014a) Studying the elusive environment in large scale. JAMA 311(21):2173–2174CrossRef
Zurück zum Zitat Patel CJ, Ioannidis JPA (2014b) Placing epidemiological results in the context of multiplicity and typical correlations of exposures. J Epidemiol Community Health 68(11):1096–1100CrossRef Patel CJ, Ioannidis JPA (2014b) Placing epidemiological results in the context of multiplicity and typical correlations of exposures. J Epidemiol Community Health 68(11):1096–1100CrossRef
Zurück zum Zitat Patel CJ, Manrai AK (2015) Development of exposome correlation globes to map out environment-wide associations. Pac Symp Biocomput 20:231–242 Patel CJ, Manrai AK (2015) Development of exposome correlation globes to map out environment-wide associations. Pac Symp Biocomput 20:231–242
Zurück zum Zitat Patel CJ, Bhattacharya J, Butte AJ (2010) An environment-wide association study (EWAS) on type 2 diabetes mellitus. PLoS One 5(5):e10746CrossRef Patel CJ, Bhattacharya J, Butte AJ (2010) An environment-wide association study (EWAS) on type 2 diabetes mellitus. PLoS One 5(5):e10746CrossRef
Zurück zum Zitat Patel CJ, Cullen MR, Ioannidis JPA, Butte AJ (2012) Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels. Int J Epidemiol 41(3):828–843CrossRef Patel CJ, Cullen MR, Ioannidis JPA, Butte AJ (2012) Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels. Int J Epidemiol 41(3):828–843CrossRef
Zurück zum Zitat Patel CJ, Rehkopf DH, Leppert JT, Bortz WM, Cullen MR, Chertow GM, Ioannidis JPA (2013) Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States national health and nutrition examination survey. Int J Epidemiol 42(6):1795–1810CrossRef Patel CJ, Rehkopf DH, Leppert JT, Bortz WM, Cullen MR, Chertow GM, Ioannidis JPA (2013) Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States national health and nutrition examination survey. Int J Epidemiol 42(6):1795–1810CrossRef
Zurück zum Zitat Patel CJ, Yang T, Zhongkai H, Wen Q, Sung J, El-Sayed YY, Cohen H et al (2014) Investigation of maternal environmental exposures in association with self-reported preterm birth. Reprod Toxicol 45:1–7CrossRef Patel CJ, Yang T, Zhongkai H, Wen Q, Sung J, El-Sayed YY, Cohen H et al (2014) Investigation of maternal environmental exposures in association with self-reported preterm birth. Reprod Toxicol 45:1–7CrossRef
Zurück zum Zitat Patel CJ, Burford B, Ioannidis JPA (2015a) Assessment of vibration of effects due to model specification can demonstrate the instability of observational associations. J Clin Epidemiol 68:1046–1058CrossRef Patel CJ, Burford B, Ioannidis JPA (2015a) Assessment of vibration of effects due to model specification can demonstrate the instability of observational associations. J Clin Epidemiol 68:1046–1058CrossRef
Zurück zum Zitat Patel CJ, Ioannidis JPA, Cullen MR, Rehkopf DH (2015b) Systematic assessment of the correlations of household income with infectious, biochemical, physiological, and environmental factors in the United States, 1999–2006. Am J Epidemiol 181(3):171–179CrossRef Patel CJ, Ioannidis JPA, Cullen MR, Rehkopf DH (2015b) Systematic assessment of the correlations of household income with infectious, biochemical, physiological, and environmental factors in the United States, 1999–2006. Am J Epidemiol 181(3):171–179CrossRef
Zurück zum Zitat Patel CJ, Ji J, Sundquist J, Ioannidis JPA, Sundquist K (2016a) Systematic assessment of pharmaceutical prescriptions in association with cancer risk: a method to conduct a population-wide medication-wide longitudinal study. Sci Rep 6:31308CrossRef Patel CJ, Ji J, Sundquist J, Ioannidis JPA, Sundquist K (2016a) Systematic assessment of pharmaceutical prescriptions in association with cancer risk: a method to conduct a population-wide medication-wide longitudinal study. Sci Rep 6:31308CrossRef
Zurück zum Zitat Patel CJ, Pho N, McDuffie M, Easton-Marks J, Kothari C, Kohane IS, Avillach P (2016c) A database of human exposomes and phenomes from the US national health and nutrition examination survey. Sci Data 3:160096CrossRef Patel CJ, Pho N, McDuffie M, Easton-Marks J, Kothari C, Kohane IS, Avillach P (2016c) A database of human exposomes and phenomes from the US national health and nutrition examination survey. Sci Data 3:160096CrossRef
Zurück zum Zitat Pearson TA, Manolio TA (2008) How to interpret a genome-wide association study. JAMA 299(11):1335–1344CrossRef Pearson TA, Manolio TA (2008) How to interpret a genome-wide association study. JAMA 299(11):1335–1344CrossRef
Zurück zum Zitat Peto R, Doll R, Buckley JD, Sporn MB (1981) Can dietary beta-carotene materially reduce human cancer rates? Nature 290:201–208CrossRef Peto R, Doll R, Buckley JD, Sporn MB (1981) Can dietary beta-carotene materially reduce human cancer rates? Nature 290:201–208CrossRef
Zurück zum Zitat Polderman TJC, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, Posthuma D (2015) Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 47:702–709CrossRef Polderman TJC, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, Posthuma D (2015) Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 47:702–709CrossRef
Zurück zum Zitat Rappaport SM (2012) Discovering environmental causes of disease. J Epidemiol Community Health 66:99–102CrossRef Rappaport SM (2012) Discovering environmental causes of disease. J Epidemiol Community Health 66:99–102CrossRef
Zurück zum Zitat Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A (2014) The blood exposome and its role in discovering causes of disease. Environ Health Perspect 122(8):769–774CrossRef Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A (2014) The blood exposome and its role in discovering causes of disease. Environ Health Perspect 122(8):769–774CrossRef
Zurück zum Zitat Schwartz D, Collins F (2007) MEDICINE: environmental biology and human disease. Science 316:695–696CrossRef Schwartz D, Collins F (2007) MEDICINE: environmental biology and human disease. Science 316:695–696CrossRef
Zurück zum Zitat Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodology 58(1):267–288 Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodology 58(1):267–288
Zurück zum Zitat Tzoulaki I, Patel CJ, Okamura T, Chan Q, Brown IJ, Miura K, Ueshima H et al (2012) A nutrient-wide association study on blood pressure. Circulation 126(21):2456–2464CrossRef Tzoulaki I, Patel CJ, Okamura T, Chan Q, Brown IJ, Miura K, Ueshima H et al (2012) A nutrient-wide association study on blood pressure. Circulation 126(21):2456–2464CrossRef
Zurück zum Zitat Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24CrossRef Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24CrossRef
Zurück zum Zitat Vittinghoff E, Glidden D, Shiboski S, McCulloch C (2005) Regression methods in biostatistics: linear, logistic, survival, and repeated measures models. Springer, New York Vittinghoff E, Glidden D, Shiboski S, McCulloch C (2005) Regression methods in biostatistics: linear, logistic, survival, and repeated measures models. Springer, New York
Zurück zum Zitat Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A et al (2014) The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–D1006CrossRef Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A et al (2014) The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–D1006CrossRef
Zurück zum Zitat Westfall PH, Stanley Young S (1993) Resampling-based multiple testing. Wiley, New York Westfall PH, Stanley Young S (1993) Resampling-based multiple testing. Wiley, New York
Zurück zum Zitat Wild CP, Scalbert A, Herceg Z (2013) Measuring the exposome: a powerful basis for evaluating environmental exposures and cancer risk. Environ Mol Mutagen 54(7):480–499CrossRef Wild CP, Scalbert A, Herceg Z (2013) Measuring the exposome: a powerful basis for evaluating environmental exposures and cancer risk. Environ Mol Mutagen 54(7):480–499CrossRef
Zurück zum Zitat Wild CP (2012) The exposome: from concept to utility. Int J Epidemiol 41(1):24–32CrossRef Wild CP (2012) The exposome: from concept to utility. Int J Epidemiol 41(1):24–32CrossRef
Zurück zum Zitat Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chu AY et al (2014) Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 46(11):1173–1186CrossRef Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chu AY et al (2014) Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 46(11):1173–1186CrossRef
Zurück zum Zitat Zou H, Hastie T (2005) Regularization and variable selection via the elastic net. J R Stat Soc Series B Stat Methodology 67:301–320CrossRef Zou H, Hastie T (2005) Regularization and variable selection via the elastic net. J R Stat Soc Series B Stat Methodology 67:301–320CrossRef
Metadaten
Titel
Exposome-Wide Association Studies: A Data-Driven Approach for Searching for Exposures Associated with Phenotype
verfasst von
Chirag J. Patel
Copyright-Jahr
2019
DOI
https://doi.org/10.1007/978-3-319-89321-1_12