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4. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

Author

Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), Pirinen, E. (Eija), Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), and Pirinen, E. (Eija)

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD⁺ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD⁺ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

Published
2023

5. Additional file 2 of Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders

Author

Auvinen, P., Vehviläinen, J., Marjonen, H., Modhukur, V., Sokka, J., Wallén, E., Rämö, K., Ahola, L., Salumets, A., Otonkoski, T., Skottman, H., Ollikainen, M., Trokovic, R., Kahila, H., and Kaminen-Ahola, N.

Abstract

Additional file 2: Figure S1. Timing and amount of maternal alcohol consumption in categories Figure S2. Characterization of hESC differentiation into germ layer cells Figure S3. Q-Q plots of genome-wide DNAm (adjusted by smoking and sex) and sensitivity analyses (adjusted by sex, maternal age, mode of delivery, and parity) Figure S4. SVD plots of sensitivity analysis for candidate genes Figure S5. PCA for PAE-associated DMPs in placenta Figure S6. Effect sizes of candidate gene DMPs in genome-wide DNAm and sensitivity analyses Figure S7. Schematic figure about PAE-associated DMR at IGF2/H19 locus in placenta Figure S8. Cell-type composition in placental samples Figure S9. GWAM comparison between control and PAE placentas Figure S10. GWAM comparison between alcohol-exposed and control hESCs Figure S11. Pathway analysis of DMPs in hESCs Figure S12. Pathway analysis of DMRs in hESCs Figure S13. Pathway analysis of differentially expressed genes in hESCs.

Published
2023
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6. An epigenome-wide association study meta-analysis of educational attainment

Author

Linnér, R Karlsson, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Consortium, B IOS, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Giles, G G, Hägg, S, Jousilahti, P, Kaprio, J, Kähönen, M, Lehtimäki, T, Martin, N G, van Meurs, J BC, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, O T, Sachdev, P S, Taskesen, E, Uitterlinden, A G, Vineis, P, Wijmenga, C, Wright, M J, Relton, C, Smith, G Davey, Deary, I J, Koellinger, P D, and Benjamin, D J

Published
2017
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10. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author

Dongen, J. Van, Hagenbeek, F.A., Suderman, M., Roetman, P.J., Sugden, K., Chiocchetti, A.G., Ismail, K., Mulder, R.H., Hafferty, J.D., Adams, M.J., Walker, R.M., Morris, S.W., Lahti, J., Küpers, L.K., Escaramis, G., Alemany, S., Bonder, M. Jan, Meijer, M., Ip, H.F., Jansen, R., Baselmans, B.M.L., Parmar, P., Lowry, E., Streit, F., Sirignano, L., Send, T.S., Frank, J., Jylhävä, J., Wang, Y., Mishra, P.P., Colins, O.F., Corcoran, D.L., Poulton, R., Mill, J., Hannon, E., Arseneault, L., Korhonen, T., Vuoksimaa, E., Felix, J.F., Bakermans-Kranenburg, M.J., Campbell, A., Czamara, D., Binder, E., Corpeleijn, E., Gonzalez, J.R., Grazuleviciene, R., Gutzkow, K.B., Evandt, J., Vafeiadi, M., Klein, M., Meer, D. van der, Ligthart, L., Kluft, C., Davies, G.E., Hakulinen, C., Keltikangas-Järvinen, L., Franke, B., Freitag, C.M., Konrad, K., Hervas, A., Fernández-Rivas, A., Vetro, A., Raitakari, O., Lehtimäki, T., Vermeiren, R., Strandberg, T., Räikkönen, K., Snieder, H., Witt, S.H., Deuschle, M., Pedersen, N.L., Hägg, S., Sunyer, J., Franke, L., Kaprio, J., Ollikainen, M., Moffitt, T.E., Tiemeier, H., van, I.M.H., Relton, C., Vrijheid, M., Sebert, S., Jarvelin, M.R., Caspi, A., Evans, K.L., McIntosh, A.M., Bartels, M., Boomsma, D.I., Dongen, J. Van, Hagenbeek, F.A., Suderman, M., Roetman, P.J., Sugden, K., Chiocchetti, A.G., Ismail, K., Mulder, R.H., Hafferty, J.D., Adams, M.J., Walker, R.M., Morris, S.W., Lahti, J., Küpers, L.K., Escaramis, G., Alemany, S., Bonder, M. Jan, Meijer, M., Ip, H.F., Jansen, R., Baselmans, B.M.L., Parmar, P., Lowry, E., Streit, F., Sirignano, L., Send, T.S., Frank, J., Jylhävä, J., Wang, Y., Mishra, P.P., Colins, O.F., Corcoran, D.L., Poulton, R., Mill, J., Hannon, E., Arseneault, L., Korhonen, T., Vuoksimaa, E., Felix, J.F., Bakermans-Kranenburg, M.J., Campbell, A., Czamara, D., Binder, E., Corpeleijn, E., Gonzalez, J.R., Grazuleviciene, R., Gutzkow, K.B., Evandt, J., Vafeiadi, M., Klein, M., Meer, D. van der, Ligthart, L., Kluft, C., Davies, G.E., Hakulinen, C., Keltikangas-Järvinen, L., Franke, B., Freitag, C.M., Konrad, K., Hervas, A., Fernández-Rivas, A., Vetro, A., Raitakari, O., Lehtimäki, T., Vermeiren, R., Strandberg, T., Räikkönen, K., Snieder, H., Witt, S.H., Deuschle, M., Pedersen, N.L., Hägg, S., Sunyer, J., Franke, L., Kaprio, J., Ollikainen, M., Moffitt, T.E., Tiemeier, H., van, I.M.H., Relton, C., Vrijheid, M., Sebert, S., Jarvelin, M.R., Caspi, A., Evans, K.L., McIntosh, A.M., Bartels, M., and Boomsma, D.I.

Abstract

Item does not contain fulltext, DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Published
2021

11. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author

Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), Boomsma, D.I. (Dorret I.), Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), and Boomsma, D.I. (Dorret I.)

Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48

Published
2021
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12. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Author

McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., Marioni R.E., McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., and Marioni R.E.

Abstract

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Result(s): Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion(s): This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Copyright © 2021, The Author(s).

Published
2021

13. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author

McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, Marioni, RE, McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, and Marioni, RE

Abstract

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Published
2021

14. Developing a spatially explicit modelling and evaluation framework for integrated carbon sequestration and biodiversity conservation: Application in southern Finland

Author

Forsius, M, Kujala, H, Minunno, F, Holmberg, M, Leikola, N, Mikkonen, N, Autio, I, Paunu, V-V, Tanhuanpaa, T, Hurskainen, P, Mayra, J, Kivinen, S, Keski-Saari, S, Kosenius, A-K, Kuusela, S, Virkkala, R, Viinikka, A, Vihervaara, P, Akujarvi, A, Back, J, Karvosenoja, N, Kumpula, T, Kuzmin, A, Makela, A, Moilanen, A, Ollikainen, M, Pekkonen, M, Peltoniemi, M, Poikolainen, L, Rankinen, K, Rasilo, T, Tuominen, S, Valkama, J, Vanhala, P, Heikkinen, RK, Forsius, M, Kujala, H, Minunno, F, Holmberg, M, Leikola, N, Mikkonen, N, Autio, I, Paunu, V-V, Tanhuanpaa, T, Hurskainen, P, Mayra, J, Kivinen, S, Keski-Saari, S, Kosenius, A-K, Kuusela, S, Virkkala, R, Viinikka, A, Vihervaara, P, Akujarvi, A, Back, J, Karvosenoja, N, Kumpula, T, Kuzmin, A, Makela, A, Moilanen, A, Ollikainen, M, Pekkonen, M, Peltoniemi, M, Poikolainen, L, Rankinen, K, Rasilo, T, Tuominen, S, Valkama, J, Vanhala, P, and Heikkinen, RK

Published
2021

15. DNA methylation signatures of aggression and closely related constructs:a meta-analysis of epigenome-wide studies across the lifespan

Author

van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), Boomsma, D. I. (Dorret, I), van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), and Boomsma, D. I. (Dorret, I)

Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Published
2021

16. Development of a forest-based bioeconomy in Finland: Insights on three value networks through expert views

Author

Korhonen, J., primary, Miettinen, J., additional, Kylkilahti, E., additional, Tuppura, A., additional, Autio, M., additional, Lähtinen, K., additional, Pätäri, S., additional, Pekkanen, T.-L., additional, Luhas, J., additional, Mikkilä, M., additional, Linnanen, L., additional, Ollikainen, M., additional, and Toppinen, A., additional

Published
2021
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21. Epigenome-wide association study of lung function level and its change

Author

Imboden, M. (Medea), Wielscher, M. (Matthias), Rezwan, F. I. (Faisal I.), Amaral, A. F. (André F.S.), Schaffner, E. (Emmanuel), Jeong, A. (Ayoung), Beckmeyer-Borowko, A. (Anna), Harris, S. E. (Sarah E.), Starr, J. M. (John M.), Deary, I. J. (Ian J.), Flexeder, C. (Claudia), Waldenberger, M. (Melanie), Peters, A. (Annette), Schulz, H. (Holger), Chen, S. (Su), Sunny, S. K. (Shadia Khan), Karmaus, W. J. (Wilfried J.J.), Jiang, Y. (Yu), Erhart, G. (Gertraud), Kronenberg, F. (Florian), Arathimos, R. (Ryan), Sharp, G. C. (Gemma C.), Henderson, A. J. (Alexander John), Fu, Y. (Yu), Piirilä, P. (Päivi), Pietiläinen, K. H. (Kirsi H.), Ollikainen, M. (Miina), Johansson, A. (Asa), Gyllensten, U. (Ulf), de Vries, M. (Maaike), van der Plaat, D. A. (Diana A.), de Jong, K. (Kim), Boezen, H. M. (H. Marike), Hall, I. P. (Ian P.), Tobin, M. D. (Martin D.), Jarvelin, M.-R. (Marjo-Riitta), Holloway, J. W. (John W.), Jarvis, D. (Deborah), Probst-Hensch, N. M. (Nicole M.), Imboden, M. (Medea), Wielscher, M. (Matthias), Rezwan, F. I. (Faisal I.), Amaral, A. F. (André F.S.), Schaffner, E. (Emmanuel), Jeong, A. (Ayoung), Beckmeyer-Borowko, A. (Anna), Harris, S. E. (Sarah E.), Starr, J. M. (John M.), Deary, I. J. (Ian J.), Flexeder, C. (Claudia), Waldenberger, M. (Melanie), Peters, A. (Annette), Schulz, H. (Holger), Chen, S. (Su), Sunny, S. K. (Shadia Khan), Karmaus, W. J. (Wilfried J.J.), Jiang, Y. (Yu), Erhart, G. (Gertraud), Kronenberg, F. (Florian), Arathimos, R. (Ryan), Sharp, G. C. (Gemma C.), Henderson, A. J. (Alexander John), Fu, Y. (Yu), Piirilä, P. (Päivi), Pietiläinen, K. H. (Kirsi H.), Ollikainen, M. (Miina), Johansson, A. (Asa), Gyllensten, U. (Ulf), de Vries, M. (Maaike), van der Plaat, D. A. (Diana A.), de Jong, K. (Kim), Boezen, H. M. (H. Marike), Hall, I. P. (Ian P.), Tobin, M. D. (Martin D.), Jarvelin, M.-R. (Marjo-Riitta), Holloway, J. W. (John W.), Jarvis, D. (Deborah), and Probst-Hensch, N. M. (Nicole M.)

Abstract

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults. In a discovery–replication EWAS design, DNAme in blood and spirometry were measured twice, 6—15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10−7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers. EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10−21 and pcombined=7.22×10−50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10−20). Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-s

Published
2019

23. Could continuous cover forestry be an economically and environmentally feasible management option on drained boreal peatlands?

Author

Nieminen, M., Hökkä, H., Laiho, R., Juutinen, A., Ahtikoski, A., Pearson, M., Kojola, S., Sarkkola, S., Launiainen, S., Valkonen, S., Penttilä, T., Lohila, A., Saarinen, M., Haahti, K., Makipää, R., Miettinen, J., Ollikainen, M., Department of Economics and Management, Markku Ollikainen / Principal Investigator, and Environmental and Resource Economics

Subjects
NORTHERN FINLAND, 4112 Forestry, ECOSYSTEM SERVICES, SEEDLING ESTABLISHMENT, SITE PREPARATION, GHG fluxes, Tree growth, Water quality, NORWAY SPRUCE FORESTS, SCOTS PINE STANDS, Regeneration, DISSOLVED ORGANIC-CARBON, Forest economics, Silviculture, SOUTHERN FINLAND, DITCH NETWORK MAINTENANCE, PHOSPHORUS EXPORT
Abstract

Environmental and economic performance of forestry on drained peatlands was reviewed to consider whether continuous cover forestry (CCF) could be a feasible alternative to even-aged management (EM). CCF was regarded feasible particularly because continuously maintaining a tree stand with significant transpiration and interception capacity would decrease the need for ditch network maintenance. Managing CCF forests in such a way that the ground water levels are lower than in clear-cut EM forests but higher than in mature EM forests could decrease greenhouse gas emissions and negative water quality impacts caused both by anoxic redox reactions and oxidation and mineralization of deep peat layers. Regeneration studies indicated potential for satisfactory natural regeneration under CCF on drained peatlands. An economic advantage in CCF over EM is that fewer investments are needed to establish the forest stand and sustain its growth. Thus, even if the growth of trees in CCF forests were lower than in EM forests, CCF could at least in some peatland sites turn out to be a more profitable forest management regime. An advantage of CCF from the viewpoint of socially optimal forest management is that it plausibly reduces the negative externalities of management compared to EM. We propose that future research in drained peatland forests should focus on assessing the economic and environmental feasibility of CCF.

Published
2018

24. Drivers of participation in gypsum treatment of fields as an innovation for water protection

Author

Kosenius, A.-K. and Ollikainen, M.

Subjects
Baltic Sea, Agricultural and Food Policy, agri-environmental policy, water protection, Land Economics/Use, gypsum application, innovation
Abstract

This paper examines the motivations of participants in a large-scale pilot project that develops a new agrienvironmental measure, gypsum treatment of arable fields, to reduce phosphorus loads to the Baltic Sea. We build a general model of crop production that allows for three motivations: profit maximization, utility from agricultural innovation, and stewardship towards the nature. They all are present in the sample, proved by farmer survey and confirmatory factor analysis. Strong profit motivation relates to large gypsumtreated area and perceived easiness of gypsum as a water protection measure, and strong environmental motivation to environmentally friendly cultivation technologies.

Published
2018
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25. Spatial model of dairy farm management, nutrient runoff and greenhouse gas emissions: Private and social optima

Author

Lotjonen, S., Temmes, E., and Ollikainen, M.

Subjects
Livestock Production/Industries
Abstract

We provide a comprehensive theoretical analysis of private and social optimum in dairy production when society accounts for greenhouse gas emissions and nutrient runoff to waterways. The private farmer maximizes revenue from milk production by choosing herd size, diet, fertilization and land allocation between crops. Changes in the diet impact milk production, manure composition, and land allocation between crops. A critical radius emerges for the choices of crops and fertilizer type (mineral and manure); it is independent of the chosen crops in the private optimum but not in the social optimum. Fertilizer intensity is higher in the manure fertilized fields than in the fields where mineral fertilizer is used. Moreover, manure application rate decreases in distance to the farm centre. In contrast to what has generally been thought, the socially optimal fertilizer application follows the same spatial pattern than the private fertilization but at a lower level of intensity. A simulation model applied to the Finnish agriculture is used to further examine the features of the model. Acknowledgement : The work presented is part of the BONUS GO4BALTIC project: . The BONUS GO4BALTIC project is supported by BONUS (Art 185), funded jointly by the EU and national funding institutions in Denmark (the Innovation Fund), Estonia (Estonian Research Council ETAG ), Finland (Academy of Finland), Poland (NCBR) and Sweden (FORMAS). The work has also received funding from Stockholm University Baltic Sea Center project Baltic Eye.

Published
2018
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26. Economics of GHG abatement strategies in Finnish mixed dairy farms

Author

Lankoski, J., Britz, W., Lotjonen, S., and Ollikainen, M.

Subjects
Agricultural and Food Policy
Abstract

We develop a theoretical framework to analyse economically optimal GHG abatement strategies for a mixed farming system with crop and dairy production. Subsequently, it is implemented as a detailed bio-economic optimization model for mixed arable-dairy farms with non-linear crop and milk yield functions and a detailed accounting of Green House Gas emissions, and parameterized to Finnish agricultural and environmental conditions. Focusing on the role of sunk costs of investments and opportunity costs of labour, we analyse optimal farm management decisions under different CO2 tax levels, considering adjustments at the extensive and intensive margin, including changes in manure storage systems and application methods. We find that the amount of GHG abatement responds more strongly to the level of sunk and opportunity costs than the CO2 tax level which underlines the relevance of the planning horizon for that type of analysis. Our findings reveal that low cost abatement options in dairy production are limited. Our model can be easily adjusted to other locations, market and policy conditions and thus provides an interesting starting point for international comparisons. Acknowledgement

Published
2018
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27. An epigenome-wide association study meta-analysis of educational attainment

Author

Karlsson Linnér, R, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Giles, G G, Hägg, S, Jousilahti, P, Kaprio, J, Kähönen, M, Lehtimäki, T, Martin, N G, van Meurs, J B C, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, O T, Sachdev, P S, Taskesen, E, Uitterlinden, A G, Vineis, P, Wijmenga, C, Wright, M J, Relton, C, Davey Smith, G, Deary, I J, Koellinger, P D, Benjamin, D J, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Stochastics, Business Web and Media, Theoretical Chemistry, Institute for Molecular Medicine Finland, University of Helsinki, Medicum, Helsinki Collegium for Advanced Studies, Department of Psychology and Logopedics, Clinicum, Department of Public Health, Department of General Practice and Primary Health Care, Johan Eriksson / Principal Investigator, HUS Abdominal Center, Developmental Psychology Research Group, Epigenetics of Complex Diseases and Traits, Genetic Epidemiology, Amsterdam Reproduction & Development (AR&D), Neurology, Applied Economics, Internal Medicine, and Erasmus MC other

Subjects
CpG Islands, DNA Methylation, Genetic Association Studies, Humans, Multifactorial Inheritance, Academic Success, Epigenesis, Genetic, Molecular Biology, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, education, Article, 3124 Neurology and psychiatry, stress, Genetic, SDG 3 - Good Health and Well-being, Journal Article, patterns, socioeconomic-status, 3112 Neurosciences, tissue, mortality, 3142 Public health care science, environmental and occupational health, age, exposure, maternal smoking, epigenetic clock, Epigenesis
Abstract

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications - in our case, CpG methylation - and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Published
2017

28. Could continuous cover forestry be an economically and environmentally feasible management option on drained boreal peatlands?

Author

Nieminen, M., primary, Hökkä, H., additional, Laiho, R., additional, Juutinen, A., additional, Ahtikoski, A., additional, Pearson, M., additional, Kojola, S., additional, Sarkkola, S., additional, Launiainen, S., additional, Valkonen, S., additional, Penttilä, T., additional, Lohila, A., additional, Saarinen, M., additional, Haahti, K., additional, Mäkipää, R., additional, Miettinen, J., additional, and Ollikainen, M., additional

Published
2018
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29. An epigenome-wide association study meta-analysis of educational attainment

Author

Karlsson Linnér, R., Marioni, R.E., Rietveld, C.A., Simpkin, A.J., Davies, N.M., Watanabe, K., Armstrong, N.J., Auro, K., Baumbach, C., Bonder, M.J., Buchwald, J., Fiorito, G., Ismail, K., Iurato, S., Joensuu, A., Karell, P., Kasela, S., Lahti, J., McRae, A.F., Mandaviya, P.R., Seppälä, I., Wang, Y., Baglietto, L., Binder, E.B., Harris, S.E., Hodge, A.M., Horvath, S., Hurme, M., Johannesson, M., Latvala, A., Mather, K.A., Medland, S.E., Metspalu, A., Milani, L., Milne, R.L., Pattie, A., Pedersen, N.L., Peters, A., Polidoro, S., Räikkönen, K., Severi, G., Starr, J.M., Stolk, L., Waldenberger, M., Eriksson, J.G., Esko, T., Franke, L., Gieger, C., Giles, G.G., Hägg, S., Jousilahti, P., Kaprio, J., Kähönen, M., Lehtimäki, T., Martin, N.G., van Meurs, J.B.C., Ollikainen, M., Perola, M., Posthuma, D., Raitakari, O.T., Sachdev, P.S., Taskesen, E., Uitterlinden, A.G., Vineis, P., Wijmenga, C., Wright, M.J., Relton, C., Davey Smith, G., Deary, I.J., Koellinger, P.D., Benjamin, D.J., Karlsson Linnér, R., Marioni, R.E., Rietveld, C.A., Simpkin, A.J., Davies, N.M., Watanabe, K., Armstrong, N.J., Auro, K., Baumbach, C., Bonder, M.J., Buchwald, J., Fiorito, G., Ismail, K., Iurato, S., Joensuu, A., Karell, P., Kasela, S., Lahti, J., McRae, A.F., Mandaviya, P.R., Seppälä, I., Wang, Y., Baglietto, L., Binder, E.B., Harris, S.E., Hodge, A.M., Horvath, S., Hurme, M., Johannesson, M., Latvala, A., Mather, K.A., Medland, S.E., Metspalu, A., Milani, L., Milne, R.L., Pattie, A., Pedersen, N.L., Peters, A., Polidoro, S., Räikkönen, K., Severi, G., Starr, J.M., Stolk, L., Waldenberger, M., Eriksson, J.G., Esko, T., Franke, L., Gieger, C., Giles, G.G., Hägg, S., Jousilahti, P., Kaprio, J., Kähönen, M., Lehtimäki, T., Martin, N.G., van Meurs, J.B.C., Ollikainen, M., Perola, M., Posthuma, D., Raitakari, O.T., Sachdev, P.S., Taskesen, E., Uitterlinden, A.G., Vineis, P., Wijmenga, C., Wright, M.J., Relton, C., Davey Smith, G., Deary, I.J., Koellinger, P.D., and Benjamin, D.J.

Abstract

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Published
2017

30. An epigenome-wide association study meta-analysis of educational attainment

Author

Karlsson Linnér, R. (R.), Marioni, R.E. (Riccardo), Rietveld, C.A. (Niels), Simpkin, A.J. (A. J.), Davies, N.M. (N. M.), Watanabe, K. (K.), Armstrong, N.J. (Nicola J.), Auro, K. (Kirsi), Baumbach, C. (Clemens), Bonder, M.J. (Marc), Buchwald, J. (J.), Fiorito, G. (G.), Ismail, K. (K.), Iurato, S. (S.), Joensuu, A. (Anni), Karell, P. (P.), Kasela, S. (Silva), Lahti, J. (Jari), McRae, A.F. (A. F.), Mandaviya, P.R. (Pooja), Seppälä, I. (Ilkka), Wang, Y. (Y.), Baglietto, L. (L.), Binder, E.B. (Elisabeth), Harris, S.E. (Sarah), Hodge, A.M. (A. M.), Horvath, S. (S.), Hurme, M. (M.), Johannesson, M. (Magnus), Latvala, A. (Antti), Mather, R., Medland, S.E. (Sarah), Metspalu, A. (A.), Milani, L. (Lili), Milne, R.L. (R. L.), Pattie, A. (Alison), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polidoro, S. (Silvia), Räikkönen, K. (Katri), Severi, G. (Gianluca), Starr, J.M. (John), Stolk, L. (Lisette), Waldenberger, M. (M.), Hagen, K. (Knut), Esko, T. (Tõnu), Franke, L. (Lude), Gieger, C. (Christian), Giles, G.G. (G. G.), Hägg, S. (Sara), Jousilahti, P. (Pekka), Kaprio, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Martin, N.G. (N. G.), Meurs, J. (J.) van, Ollikainen, M. (M.), Perola, M. (M.), Posthuma, D. (Danielle), Raitakari, O.T. (O. T.), Sachdev, P.S. (Perminder), Taskesen, E. (Erdogan), Uitterlinden, A.G. (André), Vineis, P. (Paolo), Wijmenga, C. (Ciska), Wright, M.J. (M. J.), Relton, C.L. (Caroline), Davey Smith, G. (G.), Deary, I.J. (Ian), Koellinger, P.D. (P. D.), Benjamin, D.J. (D. J.), Karlsson Linnér, R. (R.), Marioni, R.E. (Riccardo), Rietveld, C.A. (Niels), Simpkin, A.J. (A. J.), Davies, N.M. (N. M.), Watanabe, K. (K.), Armstrong, N.J. (Nicola J.), Auro, K. (Kirsi), Baumbach, C. (Clemens), Bonder, M.J. (Marc), Buchwald, J. (J.), Fiorito, G. (G.), Ismail, K. (K.), Iurato, S. (S.), Joensuu, A. (Anni), Karell, P. (P.), Kasela, S. (Silva), Lahti, J. (Jari), McRae, A.F. (A. F.), Mandaviya, P.R. (Pooja), Seppälä, I. (Ilkka), Wang, Y. (Y.), Baglietto, L. (L.), Binder, E.B. (Elisabeth), Harris, S.E. (Sarah), Hodge, A.M. (A. M.), Horvath, S. (S.), Hurme, M. (M.), Johannesson, M. (Magnus), Latvala, A. (Antti), Mather, R., Medland, S.E. (Sarah), Metspalu, A. (A.), Milani, L. (Lili), Milne, R.L. (R. L.), Pattie, A. (Alison), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polidoro, S. (Silvia), Räikkönen, K. (Katri), Severi, G. (Gianluca), Starr, J.M. (John), Stolk, L. (Lisette), Waldenberger, M. (M.), Hagen, K. (Knut), Esko, T. (Tõnu), Franke, L. (Lude), Gieger, C. (Christian), Giles, G.G. (G. G.), Hägg, S. (Sara), Jousilahti, P. (Pekka), Kaprio, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Martin, N.G. (N. G.), Meurs, J. (J.) van, Ollikainen, M. (M.), Perola, M. (M.), Posthuma, D. (Danielle), Raitakari, O.T. (O. T.), Sachdev, P.S. (Perminder), Taskesen, E. (Erdogan), Uitterlinden, A.G. (André), Vineis, P. (Paolo), Wijmenga, C. (Ciska), Wright, M.J. (M. J.), Relton, C.L. (Caroline), Davey Smith, G. (G.), Deary, I.J. (Ian), Koellinger, P.D. (P. D.), and Benjamin, D.J. (D. J.)

Abstract

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications - in our case, CpG methylation - and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Published
2017
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31. An epigenome-wide association study meta-analysis of educational attainment

Author

Linner, RK, Marioni, RE, Rietveld, Niels, Simpkin, AJ, Davies, NM, Watanabe, K, Armstrong, NJ, Auro, K, Baumbach, C, Bonder, MJ, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, Mcrae, AF, Mandaviya, Pooja, Seppala, I, Wang, Y, Baglietto, L, Binder, EB, Harris, SE, Hodge, AM, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, KA, Medland, SE, Metspalu, A, Milani, L, Milne, RL, Pattie, A, Pedersen, NL, Peters, A, Polidoro, S, Raikkonen, K, Severi, G, Starr, JM, Stolk, Lisette, Waldenberger, M, Eriksson, JG, Esko, T, Franke, L, Gieger, C, Giles, GG, Hagg, S, Jousilahti, P, Kaprio, J, Kahonen, M, Lehtimaki, T, Martin, NG, van Meurs, Joyce, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, OT, Sachdev, PS, Taskesen, E, Uitterlinden, André, Vineis, P, Wijmenga, C, Wright, MJ, Relton, C, Smith, GD, Deary, IJ, Koellinger, PD, Benjamin, DJ, Linner, RK, Marioni, RE, Rietveld, Niels, Simpkin, AJ, Davies, NM, Watanabe, K, Armstrong, NJ, Auro, K, Baumbach, C, Bonder, MJ, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, Mcrae, AF, Mandaviya, Pooja, Seppala, I, Wang, Y, Baglietto, L, Binder, EB, Harris, SE, Hodge, AM, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, KA, Medland, SE, Metspalu, A, Milani, L, Milne, RL, Pattie, A, Pedersen, NL, Peters, A, Polidoro, S, Raikkonen, K, Severi, G, Starr, JM, Stolk, Lisette, Waldenberger, M, Eriksson, JG, Esko, T, Franke, L, Gieger, C, Giles, GG, Hagg, S, Jousilahti, P, Kaprio, J, Kahonen, M, Lehtimaki, T, Martin, NG, van Meurs, Joyce, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, OT, Sachdev, PS, Taskesen, E, Uitterlinden, André, Vineis, P, Wijmenga, C, Wright, MJ, Relton, C, Smith, GD, Deary, IJ, Koellinger, PD, and Benjamin, DJ

Abstract

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10?767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Published
2017

33. Neuregulin signaling pathway in smoking behavior

Author

Gupta, R, primary, Qaiser, B, additional, He, L, additional, Hiekkalinna, T S, additional, Zheutlin, A B, additional, Therman, S, additional, Ollikainen, M, additional, Ripatti, S, additional, Perola, M, additional, Salomaa, V, additional, Milani, L, additional, Cannon, T D, additional, Madden, P A F, additional, Korhonen, T, additional, Kaprio, J, additional, and Loukola, A, additional

Published
2017
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35. Financing biodiversity in private forests. The METSO programme in Finland

Author

Ollikainen, M. and Service irevues, irevues

Subjects
ECONOMIE FORESTIERE, FORET PRIVEE, BIODIVERSITE, FONCTIONS MULTIPLES DE LA FORET, FINLANDE, [SDV.SA.SF] Life Sciences [q-bio]/Agricultural sciences/Silviculture, forestry, FINANCEMENT
Abstract

Payments for ecosystem services could be a mean to increase the maintenance and provision of ecosystem services, which otherwise would provide a too low return to forest landowners. This paper examines the recent experience from applying bidding sytems for forest biodiversity, in Finland. The Finnish Metso programme is an example of voluntary bidding systems, which are mediated by the government and are capable to encourage participation of conservation-minded forest landowners.

Published
2011

36. Financement de la biodiversité dans les forêts privées : l'exemple du programme METSO en Finlande

Author

Ollikainen, M. and Service irevues, irevues

Subjects
ECONOMIE FORESTIERE, FORET PRIVEE, BIODIVERSITE, FONCTIONS MULTIPLES DE LA FORET, FINLANDE, [SDV.SA.SF] Life Sciences [q-bio]/Agricultural sciences/Silviculture, forestry, FINANCEMENT
Abstract

Le paiement des services rendus par les écosystèmes peut être un moyen d'augmenter la pérennité et la fourniture de ces services écosystémiques qui, autrement, auraient un rendement trop faible pour de nombreux propriétaires forestiers. Cet article présente une expérience récente, réalisée en Finlande, d'application d'un système d'appel d'offres pour la biodiversité des forêts. Le programme finlandais Metso est un exemple de systèmes d'enchères volontaires, coordonnées par le gouvernement et capables d'encourager la participation des propriétaires forestiers soucieux de la conservation.

Published
2011

38. DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs

Author

Pietiläinen, K H, primary, Ismail, K, additional, Järvinen, E, additional, Heinonen, S, additional, Tummers, M, additional, Bollepalli, S, additional, Lyle, R, additional, Muniandy, M, additional, Moilanen, E, additional, Hakkarainen, A, additional, Lundbom, J, additional, Lundbom, N, additional, Rissanen, A, additional, Kaprio, J, additional, and Ollikainen, M, additional

Published
2015
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39. Saddles and bifurcations in an overlapping generations economy with a renewable resource

Author

Koskela, E. (Erkki), Ollikainen, M. (Markku), and Puhakka, M. (Mikko)

Subjects
bifurcation, overlapping generations, renewable resources
Abstract

We incorporate a renewable resource as a factor of production and store of value into an overlapping generations model. We characterize dynamics and stability of steady state equilibria by introducing the concave resource growth function. The nature of equilibria in the presence of ’well-behaved’ resource stock growth depends on the size of the intertemporal elasticity of substitution in consumption. If it is at least half, but not exactly one, steady states are saddle points. For intertemporal elasticity less than one half we use a parametric example with logistic growth to demonstrate the existence of stable equilibria (indeterminacy) and a subcritical bifurcation.

Published
2008

40. Combining ecological and economic assessment of waste management options : case newspaper

Author

Dahlbo, H., Ollikainen, M., Peltola, S., Myllymaa, T., Melanen, M., Department of Economics and Management, Taloustieteen laitos, and Ekonomi, Institutionen för

Subjects
social cost, energy recovery, energiakäyttö, jätehuolto, recycling, LCIA, economic analysis, newspapers, kaatopaikat, incineration, life cycle impact assessment, waste management, landfills, sanomalehdet, kierrätys
Published
2005

42. Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance

Author

Martino, D, Loke, YJ, Gordon, L, Ollikainen, M, Cruickshank, MN, Saffery, R, Craig, JM, Martino, D, Loke, YJ, Gordon, L, Ollikainen, M, Cruickshank, MN, Saffery, R, and Craig, JM

Abstract

BACKGROUND: The extent to which development- and age-associated epigenetic changes are influenced by genetic, environmental and stochastic factors remains to be discovered. Twins provide an ideal model with which to investigate these influences but previous cross-sectional twin studies provide contradictory evidence of within-pair epigenetic drift over time. Longitudinal twin studies can potentially address this discrepancy. RESULTS: In a pilot, genome-scale study of DNA from buccal epithelium, a relatively homogeneous tissue, we show that one-third of the CpGs assayed show dynamic methylation between birth and 18 months. Although all classes of annotated genomic regions assessed show an increase in DNA methylation over time, probes located in intragenic regions, enhancers and low-density CpG promoters are significantly over-represented, while CpG islands and high-CpG density promoters are depleted among the most dynamic probes. Comparison of co-twins demonstrated that within-pair drift in DNA methylation in our cohort is specific to a subset of pairs, who show more differences at 18 months. The rest of the pairs show either minimal change in methylation discordance, or more similar, converging methylation profiles at 18 months. As with age-associated regions, sites that change in their level of within-pair discordance between birth and 18 months are enriched in genes involved in development, but the average magnitude of change is smaller than for longitudinal change. CONCLUSIONS: Our findings suggest that DNA methylation in buccal epithelium is influenced by non-shared stochastic and environmental factors that could reflect a degree of epigenetic plasticity within an otherwise constrained developmental program.

Published
2013

43. Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss

Author

Bollepalli, S, Kaye, S, Heinonen, S, Kaprio, J, Rissanen, A, Virtanen, K A, Pietiläinen, K H, and Ollikainen, M

Abstract

Background:Few studies have examined both gene expression and DNA methylation profiles in subcutaneous adipose tissue (SAT) during long-term weight loss. Thus, molecular mechanisms in weight loss and regain remain elusive.Participants/Methods:We performed a 1-year weight loss intervention on 19 healthy obese participants (mean body mass index (BMI) 34.6?kg?m-2) and studied longitudinal gene expression (Affymetrix Human Genome U133 Plus 2.0) and DNA methylation (Infinium HumanMethylation450 BeadChip) in SAT at 0, 5 and 12 months. To examine whether weight loss and acquired obesity produce reciprocal profiles, we verified our findings in 26 BMI-discordant monozygotic twin pairs.Results:We found altered expression of 69 genes from 0 to 5’ months (short-term) weight loss. Sixty of these genes showed reversed expression in acquired obesity (twins). Altogether 21/69 genes showed significant expression–DNA methylation correlations. Pathway analyses revealed increased high-density lipoprotein-mediated lipid transport characteristic to short-term weight loss. After the fifth month, two groups of participants evolved: weight losers (WLs) and weight regainers (WRs). In WLs five genes were differentially expressed in 5 vs 12 months, three of which significantly correlated with methylation. Signaling by insulin receptor pathway showed increased expression. We further identified 35 genes with differential expression in WLs from 0 to 12 months (long-term) weight loss, with 20 showing opposite expression patterns in acquired obesity, and 16/35 genes with significant expression–DNA methylation correlations. Pathway analyses demonstrated changes in signal transduction, metabolism, immune system and cell cycle. Notably, seven genes (UCHL1, BAG3, TNMD, LEP, BHMT2, EPDR1 and OSTM1) were found to be downregulated during both short- and long-term weight loss.Conclusions:Our study indicates short- and long-term weight loss influences in transcription and DNA methylation in SAT of healthy participants. Moreover, we demonstrate that same genes react in an opposite manner in weight loss and acquired obesity.

Published
2018
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44. Cohort profile: The Peri/post-natal Epigenetic Twins Study

Author

Saffery, R, Morley, R, Carlin, JB, Joo, JHE, Ollikainen, M, Novakovic, B, Andronikos, R, Li, X, Loke, YJ, Carson, N, Wallace, EM, Umstad, MP, Permezel, M, Galati, JC, Craig, Jeffrey, Saffery, R, Morley, R, Carlin, JB, Joo, JHE, Ollikainen, M, Novakovic, B, Andronikos, R, Li, X, Loke, YJ, Carson, N, Wallace, EM, Umstad, MP, Permezel, M, Galati, JC, and Craig, Jeffrey

Published
2012

45. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

Author

Gordon, L, Joo, JE, Powel, JE, Ollikainen, M, Novakovic, B, Li, X, Andronikos, R, Cruickshank, MN, Conneely, KN, Smith, AK, Alisch, RS, Morley, R, Visscher, PM, Craig, JM, Saffery, R, Gordon, L, Joo, JE, Powel, JE, Ollikainen, M, Novakovic, B, Li, X, Andronikos, R, Cruickshank, MN, Conneely, KN, Smith, AK, Alisch, RS, Morley, R, Visscher, PM, Craig, JM, and Saffery, R

Abstract

Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

Published
2012

48. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status.

Author

Oliveira, C., Westra, J., Arango, D., Ollikainen, M., Domingo, E., Ferreira, A., Velho, S., Niessen, R., Lagerstedt, K., Alhopuro, P., Laiho, P., Veiga, I., Teixeira, M.R., Ligtenberg, M.J.L., Kleibeuker, J.H., Sijmons, R.H., Plukker, J.T., Imai, K., Lage, P., Hamelin, R., Albuquerque, C., Schwartz Jr, S., Lindblom, A., Peltomaki, P., Yamamoto, H., Aaltonen, L.A., Seruca, R., Hofstra, R.M., Oliveira, C., Westra, J., Arango, D., Ollikainen, M., Domingo, E., Ferreira, A., Velho, S., Niessen, R., Lagerstedt, K., Alhopuro, P., Laiho, P., Veiga, I., Teixeira, M.R., Ligtenberg, M.J.L., Kleibeuker, J.H., Sijmons, R.H., Plukker, J.T., Imai, K., Lage, P., Hamelin, R., Albuquerque, C., Schwartz Jr, S., Lindblom, A., Peltomaki, P., Yamamoto, H., Aaltonen, L.A., Seruca, R., and Hofstra, R.M.

Abstract

Contains fulltext : 57104.pdf (publisher's version ) (Closed access), In sporadic colorectal tumours the BRAFV600E is associated with microsatellite instability (MSI-H) and inversely associated to KRAS mutations. Tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients carrying germline mutations in hMSH2 or hMLH1 do not show BRAFV600E, however no consistent data exist regarding KRAS mutation frequency and spectrum in HNPCC tumours. We investigated KRAS in 158 HNPCC tumours from patients with germline hMLH1, hMSH2 or hMSH6 mutations, 166 MSI-H and 688 microsatellite stable (MSS) sporadic carcinomas. All tumours were characterized for MSI and 81 of 166 sporadic MSI-H colorectal cancer (CRCs) were analysed for hMLH1 promoter hypermethylation. KRAS mutations were observed in 40% of HNPCC tumours, and the mutation frequency varied upon the mismatch repair gene affected: 48% (29/61) in hMSH2, 32% (29/91) in hMLH1 and 83% (5/6) in hMSH6 (P = 0.01). KRAS mutation frequency was different between HNPCC, MSS and MSI-H CRCs (P = 0.002), and MSI-H with hMLH1 hypermethylation (P = 0.005). Furthermore, HNPCC CRCs had more G13D mutations than MSS (P < 0.0001), MSI-H (P = 0.02) or MSI-H tumours with hMLH1 hypermethylation (P = 0.03). HNPCC colorectal and sporadic MSI-H tumours without hMLH1 hypermethylation shared similar KRAS mutation frequency, in particular G13D. In conclusion, we show that depending on the genetic/epigenetic mechanism leading to MSI-H, the outcome in terms of oncogenic activation may be different, reinforcing the idea that HNPCC, sporadic MSI-H (depending on the hMLH1 status) and MSS CRCs, may target distinct kinases within the RAS/RAF/MAPK pathway.

Published
2004

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