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5. Assessment of Coronavirus Disease 2019 Intervention Strategies in the Nordic Countries Using Genomic Epidemiology.

Author

Duchene, S, Featherstone, L, Freiesleben de Blasio, B, Holmes, EC, Bohlin, J, Pettersson, JHO, Duchene, S, Featherstone, L, Freiesleben de Blasio, B, Holmes, EC, Bohlin, J, and Pettersson, JHO

Abstract

We explored how the duration, size, and number of virus transmission clusters, defined as country-specific monophyletic groups in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic tree, differed among the Nordic countries of Norway, Sweden, Denmark, Finland, and Iceland. Our results suggest that although geographical connectivity, population density, and openness influence the spread and the size of SARS-CoV-2 transmission clusters, the different country-specific intervention strategies had the largest impact. We also found a significant positive association between the size and duration of transmission clusters in the Nordic countries, suggesting that the rapid deployment of contact tracing is a key response measure in reducing virus transmission.

Published
2022

7. Designing the self-assembly of arbitrary shapes using minimal complexity building blocks

Author

Bohlin, J, Turberfield, AJ, Louis, AA, and Šulc, P

Subjects
Statistical Mechanics (cond-mat.stat-mech), General Engineering, General Physics and Astronomy, Soft Condensed Matter (cond-mat.soft), FOS: Physical sciences, General Materials Science, Computational Physics (physics.comp-ph), Condensed Matter - Soft Condensed Matter, Physics - Computational Physics, Condensed Matter - Statistical Mechanics
Abstract

The design space for a self-assembled multicomponent objects ranges from a solution in which every building block is unique to one with the minimum number of distinct building blocks that unambiguously define the target structure. Using a novel pipeline, we explore the design spaces for a set of structures of various sizes and complexities. To understand the implications of the different solutions, we analyse their assembly dynamics using patchy particle simulations and study the influence of the number of distinct building blocks and the angular and spatial tolerances on their interactions on the kinetics and yield of the target assembly. We show that the resource-saving solution with minimum number of distinct blocks can often assemble just as well (or faster) than designs where each building block is unique. We further use our methods to design multifarious structures, where building blocks are shared between different target structures. Finally, we use coarse-grained DNA simulations to investigate the realisation of multicomponent shapes using DNA nanostructures as building blocks., 12 pages

Published
2022
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9. Amplification of the epigenetic (gestational) age acceleration signal

Author

Bohlin J and Lee Y

Subjects
Oncology, medicine.medical_specialty, business.industry, Gestational age, Regression, symbols.namesake, Bonferroni correction, CpG site, Lasso (statistics), Internal medicine, Multiple comparisons problem, Principal component analysis, symbols, Medicine, Epigenetics, business
Abstract

BackgroundEpigenetic (gestational) age acceleration (E(G)AA) is associated with environmental exposures and health outcomes in humans. However, E(G)AA is the residual term from a regression of epigenetic age (outcome) on chronological (gestational) age (predictor) and therefore strongly obscured by ‘noise’ from multiple sources. Here, we propose a simple procedure, based on regression, principal component analysis (PCA), and the Lasso, that amplifies E(G)AA signals. More specifically, we first regress given (gestational) age against each CpG used for epigenetic (gestational) age prediction. The CpGs are typically taken from one of several epigenetic clocks available. PCA is subsequently performed on the resulting matrix of residual vectors for each CpG as it projects the E(G)AA signal onto perpendicular principal components (PCs), thereby separating ‘signal’ from noise. Finally, we use the Lasso to select PCs associated with an outcome of interest. We apply our method to previous studies: EAA in patients with Down’s syndrome and Werner’s syndrome and EGAA of newborns exposed to prenatal smoking as well as associations with maternal BMI.ResultsThe extracted EAA components computed using our proposed procedure revealed a significant association with Down’s syndrome (PBBBBConclusionsOur findings suggest that our proposed procedure leads to a remarkable amplification of the E(G)AA signal. Furthermore, our method reveals that E(G)AA is a composite signal that can be driven by multiple independent factors.

Published
2021

11. The impact of public health interventions in the Nordic countries during the first year of SARS-CoV-2 transmission and evolution

Author

Duchene, S, Featherstone, L, de Blasio, BF, Holmes, EC, Bohlin, J, Pettersson, JH-O, Duchene, S, Featherstone, L, de Blasio, BF, Holmes, EC, Bohlin, J, and Pettersson, JH-O

Abstract

BackgroundMany countries have attempted to mitigate and control COVID-19 through non-pharmaceutical interventions, particularly with the aim of reducing population movement and contact. However, it remains unclear how the different control strategies impacted the local phylodynamics of the causative SARS-CoV-2 virus.AimWe aimed to assess the duration of chains of virus transmission within individual countries and the extent to which countries exported viruses to their geographical neighbours.MethodsWe analysed complete SARS-CoV-2 genomes to infer the relative frequencies of virus importation and exportation, as well as virus transmission dynamics, in countries of northern Europe. We examined virus evolution and phylodynamics in Denmark, Finland, Iceland, Norway and Sweden during the first year of the COVID-19 pandemic.ResultsThe Nordic countries differed markedly in the invasiveness of control strategies, which we found reflected in transmission chain dynamics. For example, Sweden, which compared with the other Nordic countries relied more on recommendation-based rather than legislation-based mitigation interventions, had transmission chains that were more numerous and tended to have more cases. This trend increased over the first 8 months of 2020. Together with Denmark, Sweden was a net exporter of SARS-CoV-2. Norway and Finland implemented legislation-based interventions; their transmission chain dynamics were in stark contrast to their neighbouring country Sweden.ConclusionSweden constituted an epidemiological and evolutionary refugium that enabled the virus to maintain active transmission and spread to other geographical locations. Our analysis reveals the utility of genomic surveillance where monitoring of active transmission chains is a key metric.

Published
2021

13. Towards Detection of Unknown GMOs

Author

Holst-Jensen, A., primary, Berdal, K. G., additional, Bertheau, Y., additional, Bohanec, M., additional, Bohlin, J., additional, Chaouachi, M., additional, Gruden, K., additional, Hamels, S., additional, Kok, E. J., additional, Krech, A., additional, Kristoffersen, A. B., additional, Laval, V., additional, Leimanis, S., additional, Løvoll, M., additional, Morisset, D., additional, Nemeth, A., additional, Papazova, N., additional, Prins, T. W., additional, Remacle, J., additional, Richl, P., additional, Ruttink, T., additional, Taverniers, I., additional, Tengs, T., additional, van Dijk, J. P., additional, Wulff, D., additional, Žel, J., additional, Zhang, H., additional, and Žnidaršič, M., additional

Published
2012
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20. A genomic view of experimental intra- and interspecies transformation of a rifampicin resistance allele into Neisseria meningitidis

Author

Alfsnes, K, Frye, SA, Eriksson, J, Eldholm, V, Bynildsrud, O, Bohlin, J, Harrison, OB, Hood, DW, Maiden, MCJ, Tonjum, T, and Ambur, OH

Subjects
Transformations, Experimental evolutions, Genome sequencings, Homologous recombinations
Abstract

The spread of antibiotic resistance within and between different bacterial populations is a major health problem on a global scale. The identification of genetic transformation in genomic data from Neisseria meningitidis, the meningococcus (Mc), and other bacteria is problematic, since similar or even identical alleles may be involved. A particular challenge in naturally transformable bacteria generally is to distinguish between common ancestry and true recombined sites in sampled genome sequences. Furthermore, the identification of recombination following experimental transformation of homologous alleles requires identifiable differences between donor and recipient, which in itself influences the propensity for homologous recombination (HR). This study identifies the distribution of HR events following intraspecies and interspecies Mc transformations of rpoB alleles encoding rifampicin resistance by whole-genome DNA sequencing and single nucleotide variant analysis. The HR events analysed were confined to the genomic region surrounding the single nucleotide genetic marker used for selection. An exponential length distribution of these recombined events was found, ranging from a few nucleotides to about 72 kb stretches. The lengths of imported sequences were on average found to be longer following experimental transformation of the recipient with genomic DNA from an intraspecies versus an interspecies donor (P

Published
2018

21. Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation

Author

Brynildsrud, OB, Pepperell, CS, Suffys, P, Grandjean, L, Monteserin, J, Debech, N, Bohlin, J, Alfsnes, K, Pettersson, JO-H, Kirkeleite, I, Fandinho, F, da Silva, MA, Perdigao, J, Portugal, I, Viveiros, M, Clark, T, Caws, M, Dunstan, S, Phan, VKT, Lopez, B, Ritacco, V, Kitchen, A, Brown, TS, van Soolingen, D, O'Neill, MB, Holt, KE, Feil, EJ, Mathema, B, Balloux, F, Eldholm, V, Brynildsrud, OB, Pepperell, CS, Suffys, P, Grandjean, L, Monteserin, J, Debech, N, Bohlin, J, Alfsnes, K, Pettersson, JO-H, Kirkeleite, I, Fandinho, F, da Silva, MA, Perdigao, J, Portugal, I, Viveiros, M, Clark, T, Caws, M, Dunstan, S, Phan, VKT, Lopez, B, Ritacco, V, Kitchen, A, Brown, TS, van Soolingen, D, O'Neill, MB, Holt, KE, Feil, EJ, Mathema, B, Balloux, F, and Eldholm, V

Abstract

On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

Published
2018

23. The Solar Probe mission

Author

Anderson, J, Goldstein, B. E, Tsurutani, B. T, Bohlin, J. D, Jones, W. V, Mellott, M. M, Burlaga, L. F, Farquhar, R, Slavin, J. A, and Suess, S. T

Subjects
Astronautics (General)
Abstract

The Solar Probe will deliver a 133.5 kg science payload into a 4 R(S) perihelion solar polar orbit to explore in situ one of the last frontiers in the solar system - the solar corona. Using a payload of 12 scientific experiments, it will be possible to answer many long-standing fundamental problems concerning the structure and dynamics of the outer solar atmosphere, including the acceleration, storage, and transport of energetic particles near the sun and in the inner heliosphere.

Published
1990

24. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Poppelaars-Monnereau, C. (Claire), Allard, C. (Catherine), Yousefi, P. (Paul), Everson, T.M. (Todd M.), Bohlin, J. (Jon), Xu, Z. (Zongli), Huang, R.-C. (Rae-Chi), Reese, S.E. (Sarah E.), Xu, C.-J. (Cheng-Jian), Baïz, N. (Nour), Hoyo, C. (Cathrine), Agha, G. (Golareh), Roy, R. (Ritu), Holloway, J. (John), Ghantous, A. (Akram), Merid, S.K. (Simon Kebede), Bakulski, K.M. (Kelly M.), Küpers, A.M. (Marlijn), Zhang, H. (Hongmei), Richmond, R.C. (Rebecca C.), Page, C.M. (Christian M.), Duijts, L. (Liesbeth), Lie, R.T. (Rolv T.), Melton, P.E. (Phillip E.), Vonk, J.M. (Judith), Nohr, C. (Christian), Williams-DeVane, C. (ClarLynda), Huen, K. (Karen), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Gonseth, S. (Semira), Rezwan, F.I. (Faisal I.), Herceg, Z. (Zdenko), Ekström, S. (Sandra), Croen, L. (Lisa), Falahi, F. (Fahimeh), Perron, P. (Patrice), Karagas, M.R. (Margaret), Quraishi, B.M. (Bilal M.), Suderman, M.J. (Matthew J.), Magnus, M.C. (Maria C.), Jaddoe, V.W.V. (Vincent), Taylor, J.A. (Jack A.), Anderson, D. (Denise), Zhao, S. (Shanshan), Smit, H.A. (Henriëtte), Josey, M.J. (Michele J.), Bradman, A. (Asa), Baccarelli, A.A. (Andrea), Bustamante, M. (Mariona), Håberg, S.E. (Siri E), Pershagen, G. (Göran), Hertz-Picciotto, I. (Irva), Newschaffer, C. (Craig), Corpeleijn, W.E. (Willemijn), Bouchard, L. (Luigi), Lawlor, D.A. (Debbie A.), Maguire, R.L. (Rachel L.), Barcellos, L.F. (Lisa), Smith, G.D. (George Davey), Eskenazi, B. (B.), Karmaus, W. (Wilfried), Marsit, C.J. (Carmen J.), Hivert, M.-F. (Marie-France), Snieder, H. (Harold), Fallin, M.D. (M. Daniele), Melén, E. (Erik), Munthe-Kaas, M.C. (Monica Cheng), Arshad, H. (Hasan), Wiemels, J. (Joseph), Annesi-Maesano, I. (Isabella), Vrijheid, M. (Martine), Oken, E. (Emily), Holland, N. (Nina), Murphy, S.K. (Susan K.), Sørensen, T.I.A. (Thorkild), Koppelman, G.H. (Gerard), Newnham, J.P. (John), Wilcox, A.J. (Allen), Nystad, W. (Wenche), London, S.J. (Stephanie J.), Felix, J.F. (Janine), Relton, C.L. (Caroline), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Poppelaars-Monnereau, C. (Claire), Allard, C. (Catherine), Yousefi, P. (Paul), Everson, T.M. (Todd M.), Bohlin, J. (Jon), Xu, Z. (Zongli), Huang, R.-C. (Rae-Chi), Reese, S.E. (Sarah E.), Xu, C.-J. (Cheng-Jian), Baïz, N. (Nour), Hoyo, C. (Cathrine), Agha, G. (Golareh), Roy, R. (Ritu), Holloway, J. (John), Ghantous, A. (Akram), Merid, S.K. (Simon Kebede), Bakulski, K.M. (Kelly M.), Küpers, A.M. (Marlijn), Zhang, H. (Hongmei), Richmond, R.C. (Rebecca C.), Page, C.M. (Christian M.), Duijts, L. (Liesbeth), Lie, R.T. (Rolv T.), Melton, P.E. (Phillip E.), Vonk, J.M. (Judith), Nohr, C. (Christian), Williams-DeVane, C. (ClarLynda), Huen, K. (Karen), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Gonseth, S. (Semira), Rezwan, F.I. (Faisal I.), Herceg, Z. (Zdenko), Ekström, S. (Sandra), Croen, L. (Lisa), Falahi, F. (Fahimeh), Perron, P. (Patrice), Karagas, M.R. (Margaret), Quraishi, B.M. (Bilal M.), Suderman, M.J. (Matthew J.), Magnus, M.C. (Maria C.), Jaddoe, V.W.V. (Vincent), Taylor, J.A. (Jack A.), Anderson, D. (Denise), Zhao, S. (Shanshan), Smit, H.A. (Henriëtte), Josey, M.J. (Michele J.), Bradman, A. (Asa), Baccarelli, A.A. (Andrea), Bustamante, M. (Mariona), Håberg, S.E. (Siri E), Pershagen, G. (Göran), Hertz-Picciotto, I. (Irva), Newschaffer, C. (Craig), Corpeleijn, W.E. (Willemijn), Bouchard, L. (Luigi), Lawlor, D.A. (Debbie A.), Maguire, R.L. (Rachel L.), Barcellos, L.F. (Lisa), Smith, G.D. (George Davey), Eskenazi, B. (B.), Karmaus, W. (Wilfried), Marsit, C.J. (Carmen J.), Hivert, M.-F. (Marie-France), Snieder, H. (Harold), Fallin, M.D. (M. Daniele), Melén, E. (Erik), Munthe-Kaas, M.C. (Monica Cheng), Arshad, H. (Hasan), Wiemels, J. (Joseph), Annesi-Maesano, I. (Isabella), Vrijheid, M. (Martine), Oken, E. (Emily), Holland, N. (Nina), Murphy, S.K. (Susan K.), Sørensen, T.I.A. (Thorkild), Koppelman, G.H. (Gerard), Newnham, J.P. (John), Wilcox, A.J. (Allen), Nystad, W. (Wenche), London, S.J. (Stephanie J.), Felix, J.F. (Janine), and Relton, C.L. (Caroline)

Abstract

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a6causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

Published
2017
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25. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, GC, Salas, LA, Monnereau, Claire, Allard, C, Yousefi, P, Everson, TM, Bohlin, J, Xu, ZL, Huang, RC, Reese, SE, Xu, CJ, Baiz, N, Hoyo, C, Agha, G, Roy, R, Holloway, JW, Ghantous, A, Merid, SK, Bakulski, KM, Kupers, LK, Zhang, HM, Richmond, Rebecca, Page, CM, Duijts, Liesbeth, Lie, RT, Melton, PE, Vonk, JM, Nohr, EA, Williams-DeVane, C, Huen, K, Rifas-Shiman, SL, Ruiz-Arenas, C, Gonseth, S, Rezwan, FI, Herceg, Z, Ekstrom, S, Croen, L, Falahi, F, Perron, P, Karagas, MR, Quraishi, BM, Suderman, M, Magnus, MC, Jaddoe, Vincent, Taylor, JA, Anderson, D, Zhao, SS, Smit, HA, Josey, MJ, Bradman, A, Baccarelli, AA, Bustamante, M, Haberg, SE, Pershagen, G, Hertz-Picciotto, I, Newschaffer, C, Corpeleijn, E, Bouchard, L, Lawlor, DA, Maguire, RL, Barcellos, LF, Smith, GD, Eskenazi, B, Karmaus, W, Marsit, CJ, Hivert, MF, Snieder, H, Fallin, MD, Melen, E, Munthe-Kaas, MC, Arshad, H, Wiemels, JL, Annesi-Maesano, I, Vrijheid, M, Oken, E, Holland, N, Murphy, SK, Sorensen, TIA, Koppelman, GH, Newnham, JP, Wilcox, AJ, Nystad, W, London, SJ, Felix, Janine, Relton, CL, Sharp, GC, Salas, LA, Monnereau, Claire, Allard, C, Yousefi, P, Everson, TM, Bohlin, J, Xu, ZL, Huang, RC, Reese, SE, Xu, CJ, Baiz, N, Hoyo, C, Agha, G, Roy, R, Holloway, JW, Ghantous, A, Merid, SK, Bakulski, KM, Kupers, LK, Zhang, HM, Richmond, Rebecca, Page, CM, Duijts, Liesbeth, Lie, RT, Melton, PE, Vonk, JM, Nohr, EA, Williams-DeVane, C, Huen, K, Rifas-Shiman, SL, Ruiz-Arenas, C, Gonseth, S, Rezwan, FI, Herceg, Z, Ekstrom, S, Croen, L, Falahi, F, Perron, P, Karagas, MR, Quraishi, BM, Suderman, M, Magnus, MC, Jaddoe, Vincent, Taylor, JA, Anderson, D, Zhao, SS, Smit, HA, Josey, MJ, Bradman, A, Baccarelli, AA, Bustamante, M, Haberg, SE, Pershagen, G, Hertz-Picciotto, I, Newschaffer, C, Corpeleijn, E, Bouchard, L, Lawlor, DA, Maguire, RL, Barcellos, LF, Smith, GD, Eskenazi, B, Karmaus, W, Marsit, CJ, Hivert, MF, Snieder, H, Fallin, MD, Melen, E, Munthe-Kaas, MC, Arshad, H, Wiemels, JL, Annesi-Maesano, I, Vrijheid, M, Oken, E, Holland, N, Murphy, SK, Sorensen, TIA, Koppelman, GH, Newnham, JP, Wilcox, AJ, Nystad, W, London, SJ, Felix, Janine, and Relton, CL

Published
2017

26. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, G., Salas, L., Monnereau, C., Allard, C., Yousefi, P., Everson, T., Bohlin, J., Xu, Z., Huang, R., Reese, S., Xu, C., Baïz, N., Hoyo, C., Agha, G., Roy, R., Holloway, J., Ghantous, A., Merid, S., Bakulski, K., Küpers, L., Zhang, H., Richmond, R., Page, C., Duijts, L., Lie, R., Melton, Phillip, Vonk, J., Nohr, E., Williams-DeVane, C., Huen, K., Rifas-Shiman, S., Ruiz-Arenas, C., Gonseth, S., Rezwan, F., Herceg, Z., Ekström, S., Croen, L., Falahi, F., Perron, P., Karagas, M., Quraishi, B., Suderman, M., Magnus, M., Jaddoe, V., Taylor, J., Anderson, D., Zhao, S., Smit, H., Josey, M., Bradman, A., Baccarelli, A., Bustamante, M., Håberg, S., Pershagen, G., Hertz-Picciotto, I., Newschaffer, C., Corpeleijn, E., Bouchard, L., Lawlor, D., Maguire, R., Barcellos, L., Smith, G., Eskenazi, B., Karmaus, W., Marsit, C., Sharp, G., Salas, L., Monnereau, C., Allard, C., Yousefi, P., Everson, T., Bohlin, J., Xu, Z., Huang, R., Reese, S., Xu, C., Baïz, N., Hoyo, C., Agha, G., Roy, R., Holloway, J., Ghantous, A., Merid, S., Bakulski, K., Küpers, L., Zhang, H., Richmond, R., Page, C., Duijts, L., Lie, R., Melton, Phillip, Vonk, J., Nohr, E., Williams-DeVane, C., Huen, K., Rifas-Shiman, S., Ruiz-Arenas, C., Gonseth, S., Rezwan, F., Herceg, Z., Ekström, S., Croen, L., Falahi, F., Perron, P., Karagas, M., Quraishi, B., Suderman, M., Magnus, M., Jaddoe, V., Taylor, J., Anderson, D., Zhao, S., Smit, H., Josey, M., Bradman, A., Baccarelli, A., Bustamante, M., Håberg, S., Pershagen, G., Hertz-Picciotto, I., Newschaffer, C., Corpeleijn, E., Bouchard, L., Lawlor, D., Maguire, R., Barcellos, L., Smith, G., Eskenazi, B., Karmaus, W., and Marsit, C.

Abstract

© The Author 2017. Published by Oxford University Press. All rights reserved. Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small ( < 0.2% per BMI unit (1 kg/m 2 ), P < 1.06 × 10 -7 ) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a6causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

Published
2017

29. 25-hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)

Author

Suderman, M., Stene, L.C., Bohlin, J., Page, C.M., Holvik, K., Parr, C.L., Magnus, M.C., Håberg, S.E., Joubert, B.R., Wu, M.C., London, S.J., Relton, C., and Nystad, W.

Subjects
2-hydroxyvitamin D, DNA methylation, Maternal Vitamin D, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, 2-Hydroxyvitamin D, Cell Biology, DNA Methylation, Biochemistry, Offspring, Endocrinology, Maternal vitamin D, Molecular Medicine, Epigenetics, Methylome, Vitamin D, Molecular Biology
Abstract

The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation.DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC).Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR > 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR

Published
2016

30. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Author

Joubert, B.R. (Bonnie), Dekker, H.T. (Herman) den, Felix, J.F. (Janine), Bohlin, J. (Jon), Ligthart, S. (Symen), Beckett, E. (Emma), Tiemeier, H.W. (Henning), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Håberg, S.E. (Siri E), Reese, S.E. (Sarah E.), Peters, M.J. (Marjolein), Kulle Andreassen, B. (Bettina), Steegers, E.A.P. (Eric), Nilsen, R.M. (Roy M.), Vollset, S.E. (Stein E.), Midttun, . (Øivind), Ueland, P.M. (Per), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Jongste, J.C. (Johan) de, Wu, M.C. (Michael), Wang, T. (Tianyuan), Peddada, S.D. (Shyamal D.), Jaddoe, V.W.V. (Vincent), Nystad, W. (Wenche), Duijts, L. (Liesbeth), London, S.J. (Stephanie J), Joubert, B.R. (Bonnie), Dekker, H.T. (Herman) den, Felix, J.F. (Janine), Bohlin, J. (Jon), Ligthart, S. (Symen), Beckett, E. (Emma), Tiemeier, H.W. (Henning), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Hofman, A. (Albert), Håberg, S.E. (Siri E), Reese, S.E. (Sarah E.), Peters, M.J. (Marjolein), Kulle Andreassen, B. (Bettina), Steegers, E.A.P. (Eric), Nilsen, R.M. (Roy M.), Vollset, S.E. (Stein E.), Midttun, . (Øivind), Ueland, P.M. (Per), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Jongste, J.C. (Johan) de, Wu, M.C. (Michael), Wang, T. (Tianyuan), Peddada, S.D. (Shyamal D.), Jaddoe, V.W.V. (Vincent), Nystad, W. (Wenche), Duijts, L. (Liesbeth), and London, S.J. (Stephanie J)

Abstract

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina" s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.

Published
2016
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31. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Author

Joubert, BR, den Dekker, Martijn, Felix, Janine, Bohlin, J, Ligthart, Symen, Beckett, E, Tiemeier, Henning, van Meurs, Joyce, Uitterlinden, André, Hofman, Bert, Haberg, SE, Reese, SE, Peters, Marjolein, Andreassen, BK, Steegers, Eric, Nilsen, RM, Vollset, SE, Midttun, O, Ueland, PM, Franco Duran, OH, Dehghan, Abbas, Jongste, Johan, Wu, MC (MengChu), Wang, TY, Peddada, SD, Jaddoe, Vincent, Nystad, W, Duijts, Liesbeth, London, SJ, Joubert, BR, den Dekker, Martijn, Felix, Janine, Bohlin, J, Ligthart, Symen, Beckett, E, Tiemeier, Henning, van Meurs, Joyce, Uitterlinden, André, Hofman, Bert, Haberg, SE, Reese, SE, Peters, Marjolein, Andreassen, BK, Steegers, Eric, Nilsen, RM, Vollset, SE, Midttun, O, Ueland, PM, Franco Duran, OH, Dehghan, Abbas, Jongste, Johan, Wu, MC (MengChu), Wang, TY, Peddada, SD, Jaddoe, Vincent, Nystad, W, Duijts, Liesbeth, and London, SJ

Published
2016

34. Shape distortion analysis of a complex shaped wing skin section

Author

Hörberg, Erik, Nyman, Tonny, Hellström, T., Rudlund, M., Bohlin, J., Berg, R., Hörberg, Erik, Nyman, Tonny, Hellström, T., Rudlund, M., Bohlin, J., and Berg, R.

Abstract

In the Clean Sky program SFWA (Smart Fixed Wing Aircraft) [1], which is a major European research program, the main objective is to develop an all-new low drag wing. This wing is aimed to significantly reduce fuel consumption and thereby contribute to a greener environment. The Clean Sky program is an important stepping stone to be able to reach the goals of the ambitious ACARE (Advisory Council for Aeronautics Research in Europe) targets. To meet the goals, a substantial part of the wing must have laminar air flow to reduce total drag of the aircraft. To achieve these goals Saab has developed a co-cured fully integrated carbon fibre upper wing-cover, including leading edge, skin, stringers and rib-feet. This complex structure highlights the needs for accurate shape distortion analysis and tool compensation, to be able to handle global distortion and local waviness of the wing during curing. Since the upper wing-cover contains more than 100 co-cured structural elements there was a great challenge to deal with this assembled structure both from an analysis point of view, and from a manufacturing standpoint. This paper covers the analysis methodology and tooling technology used, to be able to produce this complex shaped wing demonstrator to the high standard required to meet the goals for the Clean Sky program SFWA. Results from the shape distortion analysis as well as the design and manufacturing concept of the final wing skin structure are demonstrated., QC 20181212

Published
2015

43. Effects of subclinical footpad dermatitis and emotional arousal on surface foot temperature recorded with infrared thermography in turkey toms (<italic>Meleagris gallopavo</italic>).

Author

Moe, R O, Bohlin, J, Flø, A, Vasdal, G, Erlandsen, H, Guneriussen, E, Sjökvist, E C, and Stubsjøen, S M

Subjects
*ANIMAL welfare, *TURKEYS, *POULTRY diseases, *SKIN inflammation, *INFRARED imaging
Abstract

Footpad dermatitis is a condition that causes lesions on the plantar surface of the footpads in growing turkeys. Potential inflammatory processes and pain associated with increasing severity of footpad dermatitis raise animal welfare concerns. This study investigated whether the temperature of the plantar surface of the foot (the footpads and the entire plantar foot including interdigital membranes) assessed with infrared thermography reflects severity of mild footpad dermatitis as assessed with a Visual Analogue Scale in 80 turkey toms at 10 weeks of age. In order to study effects of a potential emotional arousal due to the testing procedures, effects of sequential testing order and duration of handling of the turkeys was included in the model. Footpad temperatures were significantly lower than foot temperatures (P < 0.001, R2 = 0.57, −3.36°C ± 0.28°C), and higher visual analogue scale scores were anti-correlated with footpad (−0.06°C ± 0.037°C) and foot temperatures (−0.07°C ± 0.066°C). Furthermore, a negative association between footpad temperature and handling time (−0.02 ± 0.0227, P = 0.048), and a non-linear association between foot and footpad temperatures and sequential testing order, were found (P<0.001). The results indicate that severity of mild footpad dermatitis as scored visually was associated with the temperatures of the plantar surface of the foot and footpads, and that thermal imaging therefore represents a novel tool for the reliable and non-invasive early detection of subclinical foot pathologies in turkeys. The association was negative, and the findings therefore indicate that potential inflammatory processes in the epidermis at this early stage of footpad dermatitis are negligible, and/or that the hyperkeratosis of the surface keratin shielded heat emission from the footpads. The associations between surface temperatures, handling time, and sequential testing order suggest an emotional arousal in response to the experimental procedures, and these factors need to be considered when applying infrared thermography in future studies of leg health in turkeys. [ABSTRACT FROM AUTHOR]

Published
2018
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50. Relative entropy differences in bacterial chromosomes, plasmids, phages and genomic islands

Author

Bohlin, J., van Passel, M.W.J., Bohlin, J., and van Passel, M.W.J.

Abstract

Background: We sought to assess whether the concept of relative entropy (information capacity), could aid our understanding of the process of horizontal gene transfer in microbes. We analyzed the differences in information capacity between prokaryotic chromosomes, genomic islands (GI), phages, and plasmids. Relative entropy was estimated using the Kullback-Leibler measure. Results: Relative entropy was highest in bacterial chromosomes and had the sequence chromosomes >GI>phage>plasmid. There was an association between relative entropy and AT content in chromosomes, phages, plasmids and GIs with the strongest association being in phages. Relative entropy was also found to be lower in the obligate intracellular Mycobacterium leprae than in the related M. tuberculosis when measured on a shared set of highly conserved genes. Conclusions: We argue that relative entropy differences reflect how plasmids, phages and GIs interact with microbial host chromosomes and that all these biological entities are, or have been, subjected to different selective pressures. The rate at which amelioration of horizontally acquired DNA occurs within the chromosome is likely to account for the small differences between chromosomes and stably incorporated GIs compared to the transient or independent replicons such as phages and plasmids

Published
2012

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