. 2019 Jun 11;10(1):2548.

doi: 10.1038/s41467-019-10461-0.

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Darina Czamara¹, Gökçen Eraslan^{2

3}, Christian M Page^{4

5}, Jari Lahti^{6

7}, Marius Lahti-Pulkkinen^{6

8}, Esa Hämäläinen⁹, Eero Kajantie^{10

11

12}, Hannele Laivuori^{13

14

15

16}, Pia M Villa¹³, Rebecca M Reynolds⁸, Wenche Nystad¹⁷, Siri E Håberg⁵, Stephanie J London¹⁸, Kieran J O'Donnell^{19

20}, Elika Garg¹⁹, Michael J Meaney^{19

20

21}, Sonja Entringer^{22

23}, Pathik D Wadhwa^{23

24}, Claudia Buss^{22

23}, Meaghan J Jones²⁵, David T S Lin²⁵, Julie L MacIsaac²⁵, Michael S Kobor²⁵, Nastassja Koen^{26

27}, Heather J Zar²⁸, Karestan C Koenen²⁹, Shareefa Dalvie²⁶, Dan J Stein^{26

27}, Ivan Kondofersky^{2

30}, Nikola S Müller², Fabian J Theis^{2

30}; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Katri Räikkönen⁶, Elisabeth B Binder^{31

32}

Collaborators, Affiliations

Collaborators

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium:
Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan

Affiliations

¹ Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany.
² Institute of Computational Biology, Helmholtz-Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
³ School of Life Sciences, Weihenstephan, Technische Universität München, Freising, 85354, Germany.
⁴ Oslo Centre for Biostatistics and Epidemiology, Research Support Unit, Oslo University Hospital, Oslo, 0372, Norway.
⁵ Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
⁶ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
⁷ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00101, Finland.
⁸ British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
⁹ HUSLAB and Department of Clinical Chemistry, Helsinki University, Helsinki, 00290, Finland.
¹⁰ Oulu University Hospital and University of Oulu, PEDEGO Research Unit, MRC Oulu, 90014, Finland.
¹¹ Hospital for Children and Adolescents, University of Helsinki and Helsinki University Hospital, Helsinki, 00029, Finland.
¹² National Institute for Health and Welfare, Helsinki, 00271, Finland.
¹³ Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital, Helsinki, 00014, Finland.
¹⁴ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, 00014, Finland.
¹⁵ Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33100, Finland.
¹⁶ Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, 33100, Finland.
¹⁷ Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, 0213, Norway.
¹⁸ Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, 20814, USA.
¹⁹ Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, H3A 2B4, QC, Canada.
²⁰ Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, H3A 0G4, QC, Canada.
²¹ Singapore Institute for Clinical Sciences, Singapore, 117609, Singapore.
²² Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, 10117, Germany.
²³ University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
²⁴ Department of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
²⁵ Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
²⁶ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, 7925, South Africa.
²⁷ South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
²⁸ Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, 7505, South Africa.
²⁹ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
³⁰ Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
³¹ Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany. binder@psych.mpg.de.
³² Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 30329, USA. binder@psych.mpg.de.

PMID: 31186427
PMCID: PMC6559955
DOI: 10.1038/s41467-019-10461-0

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Darina Czamara et al. Nat Commun. 2019.

. 2019 Jun 11;10(1):2548.

doi: 10.1038/s41467-019-10461-0.

Authors

Collaborators

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium:
Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan

Affiliations

¹ Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany.
² Institute of Computational Biology, Helmholtz-Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
³ School of Life Sciences, Weihenstephan, Technische Universität München, Freising, 85354, Germany.
⁴ Oslo Centre for Biostatistics and Epidemiology, Research Support Unit, Oslo University Hospital, Oslo, 0372, Norway.
⁵ Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
⁶ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
⁷ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00101, Finland.
⁸ British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
⁹ HUSLAB and Department of Clinical Chemistry, Helsinki University, Helsinki, 00290, Finland.
¹⁰ Oulu University Hospital and University of Oulu, PEDEGO Research Unit, MRC Oulu, 90014, Finland.
¹¹ Hospital for Children and Adolescents, University of Helsinki and Helsinki University Hospital, Helsinki, 00029, Finland.
¹² National Institute for Health and Welfare, Helsinki, 00271, Finland.
¹³ Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital, Helsinki, 00014, Finland.
¹⁴ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, 00014, Finland.
¹⁵ Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33100, Finland.
¹⁶ Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, 33100, Finland.
¹⁷ Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, 0213, Norway.
¹⁸ Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, 20814, USA.
¹⁹ Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, H3A 2B4, QC, Canada.
²⁰ Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, H3A 0G4, QC, Canada.
²¹ Singapore Institute for Clinical Sciences, Singapore, 117609, Singapore.
²² Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, 10117, Germany.
²³ University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
²⁴ Department of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
²⁵ Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
²⁶ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, 7925, South Africa.
²⁷ South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
²⁸ Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, 7505, South Africa.
²⁹ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
³⁰ Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
³¹ Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany. binder@psych.mpg.de.
³² Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 30329, USA. binder@psych.mpg.de.

PMID: 31186427
PMCID: PMC6559955
DOI: 10.1038/s41467-019-10461-0

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

PubMed Disclaimer

Conflict of interest statement

E.B.B. is co-inventor on the following patent applications: FKBP5: a novel target for antidepressant therapy. European Patent# EP 1687443 B1; Polymorphisms in ABCB1 associated with a lack of clinical response to medicaments. United States Patent # 8030033; Means and methods for diagnosing predisposition for treatment emergent suicidal ideation (TESI). European application number: 08016477.5 International application number: PCT/EP2009/061575. The remaining authors declare no competing interests.

Figures

**Fig. 2**
VMR analysis in pruned PREDO I dataset. a Percentage of models (G, E, GxE or G + E) with the lowest AIC explaining variable DNA methylation using the PREDO I dataset with pruned SNPs. b Distribution of the different types of prenatal environment included in the E model with the lowest AIC (right), in the combinations yielding the best model GxE (middle), or the best model G + E models (left). To increase readability all counts <3% have been omitted. c DeltaAIC, i.e, the difference in AIC, between best model and next best model, stratified by the best model. Y-axis denotes the delta AIC and the X-axis the different models. The median is depicted by a black line, the rectangle spans the first quartile to the third quartile, whiskers above and below the box show the location of minimum and maximum beta-values. P-values are based on Wilcoxon-tests

**Fig. 3**
VMR analysis in DeepSEA annotated SNPs in PREDO I dataset. a Percentage of models (G, E, GxE or G + E) with the lowest AIC explaining variable DNA methylation using the PREDO I dataset with DeepSEA annotated SNPs. b Distribution of the locations of all VMRs and tagVMRs with best model E, G, G + E and GxE on the 450k array using only DeepSEA variants in relationship to CpG-Islands based on the Illumina 450 K annotation. c Distribution of gene-centric locations of all VMRs and tagVMRs with best model E, G, G + E and GxE on the 450k array using only DeepSEA variants

**Fig. 4**
Functional annotation of VMR-mapping in DeepSEA annotated SNPs in PREDO I dataset. a Histone mark enrichment for all VMRs. The Y-axis denotes the fold enrichment/depletion as compared to no-VMRs. Blue bars indicate significant enrichment/depletion, grey bars non-significant differences based on Fisher-tests. b Histone mark enrichment for tagVMRs with best model E, G, G + E and GxE relative to all VMRs. Green colour indicates depletion, red colour indicates enrichment. Thick black lines around the rectangles indicate significant enrichment/depletion based on Fisher-tests. c Histone mark enrichment for all DeepSEA variants in the dataset. Blue bars indicate significant enrichment/depletion based on Fisher-tests. d Histone mark enrichment for all DeepSEA variants involved in models where either G, G + E or GxE is the best model as compared to all tested DeepSEA variants. Green colour indicates depletion, red colour indicates enrichment. Thick black lines around the rectangles indicate significant enrichment/depletion based on Fisher-tests

**Fig. 5**
VMR analysis in PREDO I and replication datasets. Percentage of models (G, E, GxE or G + E) with the lowest AIC explaining variable DNA methylation in PREDO I (450 K), DCHS I (450 K), PREDO II (EPIC), UCI (EPIC) and DCHS II (EPIC)

**Fig. 6**
Consistency of best models across cohorts. Percentage of consistent best models in overlapping tag CpGs of PREDO I (450 K), DCHS I (450 K), PREDO II (EPIC), UCI (EPIC) and DCHS II (EPIC). Overlapping VMRs included significantly more CpGs as compared to all VMRs (p < 2.2 × 10⁻¹⁶, Wilcoxon-test, mean = 4.43)

**Fig. 7**
Enrichment of DeepSEA variants for GWAS associations. a Enrichment for nominal significant GWAS associations for all tested DeepSEA variants and their LD proxies for GWAS for ADHD (attention-deficit hyperactivity disorder), ASD (autism spectrum disorder), BMI (body mass index), BP (bipolar disorder), CrossDisorder, IBD (inflammatory bowel disease), MDD (major depressive disorder), SCZ (schizophrenia) and T2D (Type 2 diabetes). The Y-axis denotes the fold enrichment with regard to non-DeepSEAvariants. Blue bars indicate significant enrichment/depletion based on Fisher-tests. b Enrichment for nominal significant GWAS hits for DeepSEA variants and their LD proxies involved in best models with G, G + E or GxE as compared to all tested DeepSEA variants. Green colour indicates depletion, red colour indicates enrichment. Thick black lines around the rectangles indicate significant enrichment/depletion based on Fisher-tests

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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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