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1. Integrative Multi-omics Analysis of Childhood Aggressive Behavior

Author

Hagenbeek, Fiona A., van Dongen, Jenny, Pool, René, Roetman, Peter J., Harms, Amy C., Hottenga, Jouke Jan, Kluft, Cornelis, Colins, Olivier F., van Beijsterveldt, Catharina E. M., Fanos, Vassilios, Ehli, Erik A., Hankemeier, Thomas, Vermeiren, Robert R. J. M., Bartels, Meike, Déjean, Sébastien, and Boomsma, Dorret I.

Published
2023
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2. Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

Author

Silventoinen, Karri, Li, Weilong, Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret I., Sørensen, Thorkild I. A., and Kaprio, Jaakko

Published
2022
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4. DNA methylation in peripheral tissues and left-handedness

Author

Odintsova, Veronika V., Suderman, Matthew, Hagenbeek, Fiona A., Caramaschi, Doretta, Hottenga, Jouke-Jan, Pool, René, Dolan, Conor V., Ligthart, Lannie, van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, de Geus, Eco J. C., Beck, Jeffrey J., Ehli, Erik A., Cuellar-Partida, Gabriel, Evans, David M., Medland, Sarah E., Relton, Caroline L., Boomsma, Dorret I., and van Dongen, Jenny

Published
2022
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5. Identical twins carry a persistent epigenetic signature of early genome programming

Author

van Dongen, Jenny, Gordon, Scott D., McRae, Allan F., Odintsova, Veronika V., Mbarek, Hamdi, Breeze, Charles E., Sugden, Karen, Lundgren, Sara, Castillo-Fernandez, Juan E., Hannon, Eilis, Moffitt, Terrie E., Hagenbeek, Fiona A., van Beijsterveldt, Catharina E. M., Jan Hottenga, Jouke, Tsai, Pei-Chien, Min, Josine L., Hemani, Gibran, Ehli, Erik A., Paul, Franziska, Stern, Claudio D., Heijmans, Bastiaan T., Slagboom, P. Eline, Daxinger, Lucia, van der Maarel, Silvère M., de Geus, Eco J. C., Willemsen, Gonneke, Montgomery, Grant W., Reversade, Bruno, Ollikainen, Miina, Kaprio, Jaakko, Spector, Tim D., Bell, Jordana T., Mill, Jonathan, Caspi, Avshalom, Martin, Nicholas G., and Boomsma, Dorret I.

Published
2021
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6. Integrative multi‐omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention‐Deficit/Hyperactivity Disorder.

Author

Hubers, Nikki, Hagenbeek, Fiona A., Pool, René, Déjean, Sébastien, Harms, Amy C., Roetman, Peter J., van Beijsterveldt, Catharina E. M., Fanos, Vassilios, Ehli, Erik A., Vermeiren, Robert R. J. M., Bartels, Meike, Hottenga, Jouke Jan, Hankemeier, Thomas, van Dongen, Jenny, and Boomsma, Dorret I.

Published
2024
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7. Integrative multi‐omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention‐Deficit/Hyperactivity Disorder

Author

Hubers, Nikki, primary, Hagenbeek, Fiona A., additional, Pool, René, additional, Déjean, Sébastien, additional, Harms, Amy C., additional, Roetman, Peter J., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Hottenga, Jouke Jan, additional, Hankemeier, Thomas, additional, van Dongen, Jenny, additional, and Boomsma, Dorret I., additional

Published
2023
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8. Triplets, birthweight, and handedness

Author

Heikkilä, Kauko, Van Beijsterveldt, Catharina E. M., Haukka, Jari, Iivanainen, Matti, Saari-Kemppainen, Aulikki, Silventoinen, Karri, Boomsma, Dorret I., Yokoyama, Yoshie, and Vuoksimaa, Eero

Published
2018

15. Genetic and Environmental Effects on the Early Motor Development as a Function of Parental Educational Attainment.

Author

YAHUA ZI, VAN BEIJSTERVELDT, CATHARINA E. M., BARTELS, MEIKE, and DE GEUS, ECO J. C.

Subjects
*EDUCATION of parents, *PARENT attitudes, *HOME environment, *RESEARCH, *GENETICS, *SAMPLE size (Statistics), *CONFIDENCE intervals, *CHILD development, *TWINS, *FUNCTIONAL assessment, *DESCRIPTIVE statistics, *RESEARCH funding, *SENSITIVITY & specificity (Statistics), *STATISTICAL correlation, *ENVIRONMENTAL exposure, *MOTOR ability, *EDUCATIONAL attainment
Abstract

Introduction: The contribution of genetic and environmental factors to individual differences in earlymotor development is still largely uncharted. This large-scale twin study establishes the genetic and environmental influences on the timing of motor milestones achievement, and it further tests whether the influences aremoderated by parental education. Methods: The twins came from families registered in the Netherlands Twin Register (NTR) from 1986 to 2016. In 30,256 complete twin pairs, mother-reported ages atwhich each twin was able to first-time roll from back to belly, sit unassisted, hands-and-knees crawl, stand up unaided, and walk independently were used to extract an early motor development factor. Parental education was dichotomized ("both parents with low/average education" vs "at least one parent with high education" with university degree as a threshold). Results: Additive genetics explained 52% of the variance inmotor development, the remaining 39%and 9% were explained by shared and nonshared environment separately. Mean age of achieving motor milestones tended to be higher in infants with high educated parents, and a moderation of parental education on the genetic and environmental variance in motor development was seen in female twins with larger heritability in the high educated parents group (64% vs 43%) paired to a lower shared environmental influence (28% vs 48%). Only 7%-8% of the variance was accounted for nonshared environmental factors, including measurement error. The pattern of results did not change when the degree of urbanicity, a correlate of parental education, was additionally considered. Conclusions: Genetic factors explain most of the individual differences in the timing of motor milestone achievement, but factors related to the shared home environment also play an important role in early motor development. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Integrative Multi-omics Analysis of Childhood Aggressive Behavior

Author

Hagenbeek, Fiona A., primary, van Dongen, Jenny, additional, Pool, René, additional, Roetman, Peter J., additional, Harms, Amy C., additional, Hottenga, Jouke Jan, additional, Kluft, Cornelis, additional, Colins, Olivier F., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Hankemeier, Thomas, additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Déjean, Sébastien, additional, and Boomsma, Dorret I., additional

Published
2022
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20. A genome-wide association study of total child psychiatric problems scores

Author

Neumann, Alexander, primary, Nolte, Ilja M., additional, Pappa, Irene, additional, Ahluwalia, Tarunveer S., additional, Pettersson, Erik, additional, Rodriguez, Alina, additional, Whitehouse, Andrew, additional, van Beijsterveldt, Catharina E. M., additional, Benyamin, Beben, additional, Hammerschlag, Anke R., additional, Helmer, Quinta, additional, Karhunen, Ville, additional, Krapohl, Eva, additional, Lu, Yi, additional, van der Most, Peter J., additional, Palviainen, Teemu, additional, St Pourcain, Beate, additional, Seppälä, Ilkka, additional, Suarez, Anna, additional, Vilor-Tejedor, Natalia, additional, Tiesler, Carla M. T., additional, Wang, Carol, additional, Wills, Amanda, additional, Zhou, Ang, additional, Alemany, Silvia, additional, Bisgaard, Hans, additional, Bønnelykke, Klaus, additional, Davies, Gareth E., additional, Hakulinen, Christian, additional, Henders, Anjali K., additional, Hyppönen, Elina, additional, Stokholm, Jakob, additional, Bartels, Meike, additional, Hottenga, Jouke-Jan, additional, Heinrich, Joachim, additional, Hewitt, John, additional, Keltikangas-Järvinen, Liisa, additional, Korhonen, Tellervo, additional, Kaprio, Jaakko, additional, Lahti, Jari, additional, Lahti-Pulkkinen, Marius, additional, Lehtimäki, Terho, additional, Middeldorp, Christel M., additional, Najman, Jackob M., additional, Pennell, Craig, additional, Power, Chris, additional, Oldehinkel, Albertine J., additional, Plomin, Robert, additional, Räikkönen, Katri, additional, Raitakari, Olli T., additional, Rimfeld, Kaili, additional, Sass, Lærke, additional, Snieder, Harold, additional, Standl, Marie, additional, Sunyer, Jordi, additional, Williams, Gail M., additional, Bakermans-Kranenburg, Marian J., additional, Boomsma, Dorret I., additional, van IJzendoorn, Marinus H., additional, Hartman, Catharina A., additional, and Tiemeier, Henning, additional

Published
2022
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21. Genetic and Environmental Stability in Attention Problems across the Lifespan: Evidence from the Netherlands Twin Register

Author

Kan, Kees-Jan, Dolan, Conor V., Nivard, Michel G., Middeldorp, Christel M., van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, and Boomsma, Dorret I.

Abstract

Objective: To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and increase the understanding of stability in AP across the lifespan as a function of genetic and environmental influences. Method: A longitudinal model was fitted on Netherlands Twin Register AP scores from 44,607 child (less than 12-year-old), adolescent (12- to 18-year-old), and adult (greater than 18-year-old) twins. Results: Mean AP showed a downward trend with age. Age-to-age correlations ranged from 0.33 (50-[greater than or equal to]60 years old) to 0.73 (10-12 years old). Stability in individual differences in AP was due to genetic and environmental factors, and change was due primarily to environmental factors. Nonadditive genetic influences were present from childhood to adulthood. Total genetic variance decreased slightly throughout aging, whereas environmental variance increased substantially with the switch from maternal to self-ratings at 12 years of age. As a result, heritability coefficients decreased from 0.70 to 0.74 in childhood (maternal ratings) to 0.51 to 0.56 in adolescence (self-ratings), and 0.40 to 0.54 in adulthood (self-ratings). In childhood, male subjects scored higher than female subjects. After the rater switch at 12 years of age, female subjects tended to score higher than male subjects. Conclusions: Stability of AP is the result of genetic and environmental stability. The decrease in estimated heritability at 12 years of age is due to an increase in occasion-specific environmental variance and likely reflects a methodologic effect. Because environmental influences have lasting effects on AP, their early detection is crucial. (Contains 2 figures and 3 tables.)

Published
2013
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25. Evidence for a Causal Association of Low Birth Weight and Attention Problems

Author

Groen-Blokhuis, Maria M., Middeldorp, Christel M., van Beijsterveldt, Catharina E. M., and Boomsma, Dorret I.

Abstract

Objective: Low birth weight (LBW) is associated with attention problems (AP) and attention-deficit/hyperactivity disorder (ADHD). The etiology of this association is unclear. We investigate whether there is a causal influence of birth weight (BW) on AP and whether the BW effect is mediated by catch-up growth (CUG) in low-BW children. Method: Longitudinal data from greater than 29,000 twins registered with the Netherlands Twin Register with BW [greater than or equal] 1,500 g and gestational age (GA) [greater than or equal] 32 weeks were analyzed with the cotwin control method. Hyperactivity and AP were assessed at ages 3, 7, 10, and 12 years; weight was assessed at birth and age 2 years. Results: Children in the lowest BW category of 1,500 to 2,000 g scored 0.18 to 0.37 standard deviations (SD) higher on AP than children in the reference category of 3,000 to 3,500 g. This effect was present in term-born and preterm-born children. Importantly, in BW discordant monozygotic (MZ), dizygotic (DZ), and unrelated (UR) pairs, the child with the lower BW scored higher on hyperactivity and AP than the child with the higher BW and within-pair differences were similar for MZ, DZ, and UR pairs. This pattern is consistent with a causal effect of BW on AP. MZ and DZ twin pairs concordant for LBW but discordant for CUG showed similar AP scores, thus ruling out any effect of CUG on AP. Conclusions: These results strongly indicate that the association of birth weight and AP represents a causal relationship. The effects of BW are not explained by CUG in LBW children. (Contains 2 figures and 3 tables.)

Published
2011
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26. Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder

Author

Hubers, Nikki, primary, Hagenbeek, Fiona A., additional, Pool, René, additional, Déjean, Sébastien, additional, Harms, Amy C., additional, Roetman, Peter J., additional, van Beijsterveldt, Catharina E. M., additional, Fanos, Vassilios, additional, Ehli, Erik A., additional, Vermeiren, Robert R. J. M., additional, Bartels, Meike, additional, Hottenga, Jouke Jan, additional, Hankemeier, Thomas, additional, van Dongen, Jenny, additional, and Boomsma, Dorret I., additional

Published
2022
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27. Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Silventoinen, Karri, Li, Weilong, Jelenkovic Moreno, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret I., Sørensen, Thorkild I. A., Kaprio, Jaakko, Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Silventoinen, Karri, Li, Weilong, Jelenkovic Moreno, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret I., Sørensen, Thorkild I. A., and Kaprio, Jaakko

Abstract

Background Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Published
2022

28. A genome-wide association study of total child psychiatric problems scores

Author

Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S., Pettersson, Erik, Rodriguez, Alina, Whitehouse, Andrew, van Beijsterveldt, Catharina E. M., Benyamin, Beben, Hammerschlag, Anke R., Helmer, Quinta, Karhunen, Ville, Krapohl, Eva, Lu, Yi, van der Most, Peter J., Palviainen, Teemu, Pourcain, Beate St, Seppälä, Ilkka, Suarez, Anna, Vilor-Tejedor, Natalia, Tiesler, Carla M. T., Wang, Carol, Wills, Amanda, Zhou, Ang, Alemany, Silvia, Bisgaard, Hans, Bønnelykke, Klaus, Davies, Gareth E., Hakulinen, Christian, Henders, Anjali K., Hyppönen, Elina, Stokholm, Jakob, Bartels, Meike, Hottenga, Jouke-Jan, Heinrich, Joachim, Hewitt, John, Keltikangas-Järvinen, Liisa, Korhonen, Tellervo, Kaprio, Jaakko, Lahti, Jari, Lahti-Pulkkinen, Marius, Lehtimäki, Terho, Middeldorp, Christel M., Najman, Jackob M., Pennell, Craig, Power, Chris, Oldehinkel, Albertine J., Plomin, Robert, Räikkönen, Katri, Raitakari, Olli T., Rimfeld, Kaili, Sass, Lærke, Snieder, Harold, Standl, Marie, Sunyer, Jordi, Williams, Gail M., Bakermans-Kranenburg, Marian J., Boomsma, Dorret I., van IJzendoorn, Marinus H., Hartman, Catharina A., Tiemeier, Henning, Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S., Pettersson, Erik, Rodriguez, Alina, Whitehouse, Andrew, van Beijsterveldt, Catharina E. M., Benyamin, Beben, Hammerschlag, Anke R., Helmer, Quinta, Karhunen, Ville, Krapohl, Eva, Lu, Yi, van der Most, Peter J., Palviainen, Teemu, Pourcain, Beate St, Seppälä, Ilkka, Suarez, Anna, Vilor-Tejedor, Natalia, Tiesler, Carla M. T., Wang, Carol, Wills, Amanda, Zhou, Ang, Alemany, Silvia, Bisgaard, Hans, Bønnelykke, Klaus, Davies, Gareth E., Hakulinen, Christian, Henders, Anjali K., Hyppönen, Elina, Stokholm, Jakob, Bartels, Meike, Hottenga, Jouke-Jan, Heinrich, Joachim, Hewitt, John, Keltikangas-Järvinen, Liisa, Korhonen, Tellervo, Kaprio, Jaakko, Lahti, Jari, Lahti-Pulkkinen, Marius, Lehtimäki, Terho, Middeldorp, Christel M., Najman, Jackob M., Pennell, Craig, Power, Chris, Oldehinkel, Albertine J., Plomin, Robert, Räikkönen, Katri, Raitakari, Olli T., Rimfeld, Kaili, Sass, Lærke, Snieder, Harold, Standl, Marie, Sunyer, Jordi, Williams, Gail M., Bakermans-Kranenburg, Marian J., Boomsma, Dorret I., van IJzendoorn, Marinus H., Hartman, Catharina A., and Tiemeier, Henning

Abstract

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Published
2022

29. Changing genetic architecture of body mass index from infancy to early adulthood:an individual based pooled analysis of 25 twin cohorts

Author

Silventoinen, Karri, Li, Weilong, Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret, Sorensen, Thorkild I. A., Kaprio, Jaakko, Silventoinen, Karri, Li, Weilong, Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret, Sorensen, Thorkild I. A., and Kaprio, Jaakko

Abstract

Background Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Published
2022

36. Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles

Author

Odintsova, Veronika V., primary, Rebattu, Valerie, additional, Hagenbeek, Fiona A., additional, Pool, René, additional, Beck, Jeffrey J., additional, Ehli, Erik A., additional, van Beijsterveldt, Catharina E. M., additional, Ligthart, Lannie, additional, Willemsen, Gonneke, additional, de Geus, Eco J. C., additional, Hottenga, Jouke-Jan, additional, Boomsma, Dorret I., additional, and van Dongen, Jenny, additional

Published
2021
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37. Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

Author

Smit, Dirk J. A., primary, Andreassen, Ole A., additional, Boomsma, Dorret I., additional, Burwell, Scott J., additional, Chorlian, David B., additional, de Geus, Eco J. C., additional, Elvsåshagen, Torbjørn, additional, Gordon, Reyna L., additional, Harper, Jeremy, additional, Hegerl, Ulrich, additional, Hensch, Tilman, additional, Iacono, William G., additional, Jawinski, Philippe, additional, Jönsson, Erik G., additional, Luykx, Jurjen J., additional, Magne, Cyrille L., additional, Malone, Stephen M., additional, Medland, Sarah E., additional, Meyers, Jacquelyn L., additional, Moberget, Torgeir, additional, Porjesz, Bernice, additional, Sander, Christian, additional, Sisodiya, Sanjay M., additional, Thompson, Paul M., additional, van Beijsterveldt, Catharina E. M., additional, van Dellen, Edwin, additional, Via, Marc, additional, and Wright, Margaret J., additional

Published
2021
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39. Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder: results of a discordant twin study

Author

Afd Pharmacology, Pharmacology, Slob, Elise M A, Brew, Bronwyn K, Vijverberg, Susanne J H, Dijs, Talitha, van Beijsterveldt, Catharina E M, Koppelman, Gerard H, Bartels, Meike, Dolan, Conor V, Larsson, Henrik, Lundström, Sebastian, Lichtenstein, Paul, Gong, Tong, Maitland-van der Zee, Anke H, Kraneveld, Aletta D, Almqvist, Catarina, Boomsma, Dorret I, Afd Pharmacology, Pharmacology, Slob, Elise M A, Brew, Bronwyn K, Vijverberg, Susanne J H, Dijs, Talitha, van Beijsterveldt, Catharina E M, Koppelman, Gerard H, Bartels, Meike, Dolan, Conor V, Larsson, Henrik, Lundström, Sebastian, Lichtenstein, Paul, Gong, Tong, Maitland-van der Zee, Anke H, Kraneveld, Aletta D, Almqvist, Catarina, and Boomsma, Dorret I

Published
2021

40. Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder : results of a discordant twin study

Author

Slob, Elise M. A., Brew, Bronwyn K., Vijverberg, Susanne J. H., Dijs, Talitha, van Beijsterveldt, Catharina E. M., Koppelman, Gerard H., Bartels, Meike, Dolan, Conor V., Larsson, Henrik, Lundström, Sebastian, Lichtenstein, Paul, Gong, Tong, Maitland-van der Zee, Anke H., Kraneveld, Aletta D., Almqvist, Catarina, Boomsma, Dorret I., Slob, Elise M. A., Brew, Bronwyn K., Vijverberg, Susanne J. H., Dijs, Talitha, van Beijsterveldt, Catharina E. M., Koppelman, Gerard H., Bartels, Meike, Dolan, Conor V., Larsson, Henrik, Lundström, Sebastian, Lichtenstein, Paul, Gong, Tong, Maitland-van der Zee, Anke H., Kraneveld, Aletta D., Almqvist, Catarina, and Boomsma, Dorret I.

Abstract

BACKGROUND: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design. METHODS: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden. RESULTS: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively). CONCLUSIONS: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics., Funding agencies:Netherlands Organization for Health Research and Development 024.001.003 Netherlands Organization for Scientific Research (NWO) 480-15-001/674 Amsterdam Public Health (APH) research instituteKNAW Academy Professor Award PAH/6635Dutch Lung Foundation 5.1.16.094AMC Young Talent FundJo Kolk Studiefonds

Published
2021
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41. Associations of sleep with psychological problems and well-being in adolescence: causality or common genetic predispositions?

Author

Vermeulen, Marije C M, van der Heijden, Kristiaan B, Kocevska, Desana, Treur, Jorien L, Huppertz, Charlotte, van Beijsterveldt, Catharina E M, Boomsma, Dorret I, Swaab, Hanna, Van Someren, Eus J W, Bartels, Meike, Vermeulen, Marije C M, van der Heijden, Kristiaan B, Kocevska, Desana, Treur, Jorien L, Huppertz, Charlotte, van Beijsterveldt, Catharina E M, Boomsma, Dorret I, Swaab, Hanna, Van Someren, Eus J W, and Bartels, Meike

Abstract

BACKGROUND: Whereas short and problematic sleep are associated with psychological problems in adolescence, causality remains to be elucidated. This study therefore utilized the discordant monozygotic cotwin design and cross-lagged models to investigate how short and problematic sleep affect psychological functioning.METHODS: Adolescent twins (N = 12,803, 13-20 years, 42% male) completed questionnaires on sleep and psychological functioning repeatedly over a two-year interval. Monozygotic twin pairs were classified as concordant or discordant for sleep duration and trouble sleeping. Resulting subgroups were compared regarding internalizing problems, externalizing problems, and subjective well-being.RESULTS: Cross-sectional analyses indicated associations of worse psychological functioning with both short sleep and problematic sleep, and cross-lagged models indicate bidirectional associations. Longitudinal analyses showed that an increase in sleep problems experienced selectively by one individual of an identical twin pair was accompanied by an increase of 52% in internalizing problem scores and 25% in externalizing problem scores. These changes were significantly different from the within-subject changes in cotwins with unchanged sleep quality (respectively, 3% increase and 5% decrease). Psychological functioning did, however, not worsen with decreasing sleep duration.CONCLUSIONS: The findings suggest that sleep quality, rather than sleep duration, should be the primary target for prevention and intervention, with possible effect on psychological functioning in adolescents.

Published
2021

42. Identical twins carry a persistent epigenetic signature of early genome programming

Author

Reversade, Bruno, van Dongen, Jenny; Gordon, Scott D.; McRae, Allan F.; Odintsova, Veronika V.; Mbarek, Hamdi; Breeze, Charles E.; Sugden, Karen; Lundgren, Sara; Castillo-Fernandez, Juan E.; Hannon, Eilis; Moffitt, Terrie E.; Hagenbeek, Fiona A.; van Beijsterveldt, Catharina E. M.; Hottenga, Jouke Jan; Tsai, Pei-Chien; Min, Josine L.; Hemani, Gibran; Ehli, Erik A.; Paul, Franziska; Stern, Claudio D.; Heijmans, Bastiaan T.; Slagboom, P. Eline; Daxinger, Lucia; van der Maarel, Silvere M.; de Geus, E. J. C.; Willemsen, Gonneke; Montgomery, Grant W.; Ollikainen, Miina; Kaprio, Jaakko; Spector, Tim D.; Bell, Jordana T.; Mill, Jonathan; Caspi, Avshalom; Martin, Nicholas G.; Boomsma, Dorret, I., School of Medicine, Reversade, Bruno, van Dongen, Jenny; Gordon, Scott D.; McRae, Allan F.; Odintsova, Veronika V.; Mbarek, Hamdi; Breeze, Charles E.; Sugden, Karen; Lundgren, Sara; Castillo-Fernandez, Juan E.; Hannon, Eilis; Moffitt, Terrie E.; Hagenbeek, Fiona A.; van Beijsterveldt, Catharina E. M.; Hottenga, Jouke Jan; Tsai, Pei-Chien; Min, Josine L.; Hemani, Gibran; Ehli, Erik A.; Paul, Franziska; Stern, Claudio D.; Heijmans, Bastiaan T.; Slagboom, P. Eline; Daxinger, Lucia; van der Maarel, Silvere M.; de Geus, E. J. C.; Willemsen, Gonneke; Montgomery, Grant W.; Ollikainen, Miina; Kaprio, Jaakko; Spector, Tim D.; Bell, Jordana T.; Mill, Jonathan; Caspi, Avshalom; Martin, Nicholas G.; Boomsma, Dorret, I., and School of Medicine

Abstract

The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues. Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin., Netherlands Organization for Scientific Research (NWO) Biobanking and Biomolecular Research Infrastructure; NWO Large Scale infrastructures, X-Omics

Published
2021

43. Parental Age and Offspring Childhood Mental Health:A Multi-Cohort, Population-Based Investigation

Author

Zondervan-Zwijnenburg, Maria A J, Veldkamp, Sabine A M, Neumann, Alexander, Barzeva, Stefania A, Nelemans, Stefanie A, van Beijsterveldt, Catharina E M, Branje, Susan J T, Hillegers, Manon H J, Meeus, Wim H J, Tiemeier, Henning, Hoijtink, Herbert J A, Oldehinkel, Albertine J, Boomsma, Dorret I, Leerstoel Hoijtink, Leerstoel Branje, Methodology and statistics for the behavioural and social sciences, Adolescent development: Characteristics and determinants, Leerstoel Hoijtink, Leerstoel Branje, Methodology and statistics for the behavioural and social sciences, Adolescent development: Characteristics and determinants, Child and Adolescent Psychiatry / Psychology, Biological Psychology, APH - Methodology, APH - Mental Health, and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Subjects
Empirical Articles, Male, Parents, Netherlands Twin Register (NTR), Offspring, DISORDERS, Child Behavior, CHILDREN, Behavioral Symptoms, Population based, Social class, 050105 experimental psychology, Education, Cohort Studies, SDG 3 - Good Health and Well-being, OLDER MATERNAL AGE, Developmental and Educational Psychology, Humans, 0501 psychology and cognitive sciences, Child, Association (psychology), Depression (differential diagnoses), Netherlands, ASSOCIATIONS, RISK, 05 social sciences, INFORMANT, DEPRESSION, Mental health, ADVANCED PATERNAL AGE, Social Class, DE-NOVO MUTATIONS, Pediatrics, Perinatology and Child Health, Cohort, Empirical Article, Female, PROBLEM BEHAVIOR, Psychology, 050104 developmental & child psychology, Demography, Cohort study
Abstract

To examine the contributions of maternal and paternal age on offspring externalizing and internalizing problems, this study analyzed problem behaviors at age 10-12 years from four Dutch population-based cohorts (N = 32,892) by a multiple informant design. Bayesian evidence synthesis was used to combine results across cohorts with 50% of the data analyzed for discovery and 50% for confirmation. There was evidence of a robust negative linear relation between parental age and externalizing problems as reported by parents. In teacher-reports, this relation was largely explained by parental socio-economic status. Parental age had limited to no association with internalizing problems. Thus, in this large population-based study, either a beneficial or no effect of advanced parenthood on child problem behavior was observed.

Published
2020

44. Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkanen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Oyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao Catalá, José Ramón, Schnurr, Theresia M., Barroso, Ines, Bonnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie Aline, Chawes, Bo, Clement, Karine, Closa Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquín, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke Jan, Hypponen, Elina, Johansson, Stefan, Joro, Raimo, Kahonen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kuehnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimaki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina Gómez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, Andre G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa Marina, Loreto, Reischl, Eva, Frithioff-Bojsoe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njolstad, Pal R., Dedoussis, George D., Froguel, Philippe, Sorensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikainen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widen, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Jarvelin, Marjo-Riitta, Koerner, Antje, Smith, George Davey, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Jaddoe, Vincent W. V., Grant, Struan F. A., Felix, Janine F., Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkanen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Oyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao Catalá, José Ramón, Schnurr, Theresia M., Barroso, Ines, Bonnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie Aline, Chawes, Bo, Clement, Karine, Closa Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquín, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke Jan, Hypponen, Elina, Johansson, Stefan, Joro, Raimo, Kahonen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kuehnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimaki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina Gómez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, Andre G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa Marina, Loreto, Reischl, Eva, Frithioff-Bojsoe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njolstad, Pal R., Dedoussis, George D., Froguel, Philippe, Sorensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikainen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widen, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Jarvelin, Marjo-Riitta, Koerner, Antje, Smith, George Davey, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Jaddoe, Vincent W. V., Grant, Struan F. A., and Felix, Janine F.

Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. O

Published
2020

45. Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education

Author

Fisiología, Genética, antropología física y fisiología animal, Fisiologia, Genetika,antropologia fisikoa eta animalien fisiologia, Jelenkovic Moreno, Aline, Sund, Reijo, Yokoyama, Yoshie, Latvala, Antti, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Freitas, Duarte L., Maia, José Antonio, Knafo Noam, Ariel, Mankuta, David, Abramson, Lior, Ji, Fuling, Ning, Feng, Pang, Zengchang, Rebato Ochoa, Esther Matilde, Saudino, Kimberly J., Cutler, Tessa L., Hopper, John L., Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Cozen, Wendy, Hwang, Amie E., Mack, Thomas M., Nelson, Tracy L., Whitfield, Keith E., Sung, Joohon, Kim, Jina, Lee, Jooyeon, Lee, Sooji, Llewellyn, Clare H., Fisher, Abigail, Medda, Emanuela, Nisticò, Lorenza, Toccaceli, Virgilia, Baker, Laura A., Tuvblad, Catherine, Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Burt, S. Alexandra, Klump, Kelly L., Silberg, Judy L., Maes, Hermine H., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Gatz, Margaret, Butler, David A., Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas S., Harden, K. Paige, Tucker-Drob, Elliot M., Franz, Carol E., Kremen, William S., Lyons, Michael J., Lichtenstein, Paul, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, Öncel, Sevgi Y., Aliev, Fazil, Jeong, Hoe-Uk, Hur, Yoon-Mi, Turkheimer, Eric, Boomsma, Dorret I., Sørensen, Thorkild I. A., Kaprio, Jaakko, Silventoinen, Karri, Fisiología, Genética, antropología física y fisiología animal, Fisiologia, Genetika,antropologia fisikoa eta animalien fisiologia, Jelenkovic Moreno, Aline, Sund, Reijo, Yokoyama, Yoshie, Latvala, Antti, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Freitas, Duarte L., Maia, José Antonio, Knafo Noam, Ariel, Mankuta, David, Abramson, Lior, Ji, Fuling, Ning, Feng, Pang, Zengchang, Rebato Ochoa, Esther Matilde, Saudino, Kimberly J., Cutler, Tessa L., Hopper, John L., Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Cozen, Wendy, Hwang, Amie E., Mack, Thomas M., Nelson, Tracy L., Whitfield, Keith E., Sung, Joohon, Kim, Jina, Lee, Jooyeon, Lee, Sooji, Llewellyn, Clare H., Fisher, Abigail, Medda, Emanuela, Nisticò, Lorenza, Toccaceli, Virgilia, Baker, Laura A., Tuvblad, Catherine, Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Burt, S. Alexandra, Klump, Kelly L., Silberg, Judy L., Maes, Hermine H., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Gatz, Margaret, Butler, David A., Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas S., Harden, K. Paige, Tucker-Drob, Elliot M., Franz, Carol E., Kremen, William S., Lyons, Michael J., Lichtenstein, Paul, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, Öncel, Sevgi Y., Aliev, Fazil, Jeong, Hoe-Uk, Hur, Yoon-Mi, Turkheimer, Eric, Boomsma, Dorret I., Sørensen, Thorkild I. A., Kaprio, Jaakko, and Silventoinen, Karri

Abstract

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

Published
2020

46. Genetic and environmental variation in educational attainment: an individual-based analysis of 28 twin cohorts

Author

Fisiología, Fisiologia, Silventoinen, Karri, Jelenkovic Moreno, Aline, Sund, Reijo, Latvala, Antti, Honda, Chika, Inui, Fujio, Tomizawa, Rie, Watanabe, Mikio, Sakai, Norio, Rebato Ochoa, Esther Matilde, Busjahn, Andreas, Tyler, Jessica, Hopper, John L., Ordoñana Martín, Juan Ramón, Sánchez Romera, Juan Francisco, Colodro Conde, Lucía, Calais Ferreira, Lucas, Oliveira, Vinicius C., Ferreira, Pablo H., Medda, Emanuela, Nisticò, Lorenza, Toccaceli, Virgilia, Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Siribaddana, Sisira H., Hotopf, Matthew, Sumathipala, Athula, Rijsdijk, Fruhling, Duncan, Glen E., Buchwald, Dedra, Tynelius, Per, Rasmussen, Finn, Tan, Qihua, Zhang, Dongfeng, Pang, Zengchang, Magnusson, Patrik K. E., Pedersen, Nancy L., Dahl Aslan, Anna K., Hwang, Amie E., Mack, Thomas M., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Brandt, Ingunn, Nilsen, Thomas S., Harris, Jennifer R., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Willemsen, Gonneke, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Franz, Carol E., Kremen, William S., Lyons, Michael J., Silberg, Judy L., Maes, Hermine H., Kandler, Christian, Nelson, Tracy L., Whitfield, Keith E., Corley, Robin P., Huibregtse, Brooke M., Gatz, Margaret, Butler, David A., Tarnoki, Adam D., Tarnoki, David L., Park, Hang A., Lee, Jooyeon, Lee, Soo Ji, Sung, Joohon, Yokoyama, Yoshie, Sørensen, Thorkild I. A., Boomsma, Dorret I., Kaprio, Jaakko, Fisiología, Fisiologia, Silventoinen, Karri, Jelenkovic Moreno, Aline, Sund, Reijo, Latvala, Antti, Honda, Chika, Inui, Fujio, Tomizawa, Rie, Watanabe, Mikio, Sakai, Norio, Rebato Ochoa, Esther Matilde, Busjahn, Andreas, Tyler, Jessica, Hopper, John L., Ordoñana Martín, Juan Ramón, Sánchez Romera, Juan Francisco, Colodro Conde, Lucía, Calais Ferreira, Lucas, Oliveira, Vinicius C., Ferreira, Pablo H., Medda, Emanuela, Nisticò, Lorenza, Toccaceli, Virgilia, Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Siribaddana, Sisira H., Hotopf, Matthew, Sumathipala, Athula, Rijsdijk, Fruhling, Duncan, Glen E., Buchwald, Dedra, Tynelius, Per, Rasmussen, Finn, Tan, Qihua, Zhang, Dongfeng, Pang, Zengchang, Magnusson, Patrik K. E., Pedersen, Nancy L., Dahl Aslan, Anna K., Hwang, Amie E., Mack, Thomas M., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Brandt, Ingunn, Nilsen, Thomas S., Harris, Jennifer R., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Willemsen, Gonneke, Bartels, Meike, Van Beijsterveldt, Catharina E. M., Franz, Carol E., Kremen, William S., Lyons, Michael J., Silberg, Judy L., Maes, Hermine H., Kandler, Christian, Nelson, Tracy L., Whitfield, Keith E., Corley, Robin P., Huibregtse, Brooke M., Gatz, Margaret, Butler, David A., Tarnoki, Adam D., Tarnoki, David L., Park, Hang A., Lee, Jooyeon, Lee, Soo Ji, Sung, Joohon, Yokoyama, Yoshie, Sørensen, Thorkild I. A., Boomsma, Dorret I., and Kaprio, Jaakko

Abstract

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a(2)=0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c(2)=0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a(2)=0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a(2)=0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c(2)=0.31; 0.29-0.33 and c(2)=0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

Published
2020

47. Content, diagnostic, correlational, and genetic similarities between common measures of childhood aggressive behaviors and related psychiatric traits

Author

Leerstoel Finkenauer, Youth in Changing Cultural Contexts, Hendriks, Anne M, Ip, Hill F, Nivard, Michel G, Finkenauer, Catrin, Van Beijsterveldt, Catharina E M, Bartels, Meike, Boomsma, Dorret I, Leerstoel Finkenauer, Youth in Changing Cultural Contexts, Hendriks, Anne M, Ip, Hill F, Nivard, Michel G, Finkenauer, Catrin, Van Beijsterveldt, Catharina E M, Bartels, Meike, and Boomsma, Dorret I

Published
2020

48. Parental Age and Offspring Childhood Mental Health: A Multi-Cohort, Population-Based Investigation

Author

Leerstoel Hoijtink, Leerstoel Branje, Methodology and statistics for the behavioural and social sciences, Adolescent development: Characteristics and determinants, Zondervan-Zwijnenburg, Maria A J, Veldkamp, Sabine A M, Neumann, Alexander, Barzeva, Stefania A, Nelemans, Stefanie A, van Beijsterveldt, Catharina E M, Branje, Susan J T, Hillegers, Manon H J, Meeus, Wim H J, Tiemeier, Henning, Hoijtink, Herbert J A, Oldehinkel, Albertine J, Boomsma, Dorret I, Leerstoel Hoijtink, Leerstoel Branje, Methodology and statistics for the behavioural and social sciences, Adolescent development: Characteristics and determinants, Zondervan-Zwijnenburg, Maria A J, Veldkamp, Sabine A M, Neumann, Alexander, Barzeva, Stefania A, Nelemans, Stefanie A, van Beijsterveldt, Catharina E M, Branje, Susan J T, Hillegers, Manon H J, Meeus, Wim H J, Tiemeier, Henning, Hoijtink, Herbert J A, Oldehinkel, Albertine J, and Boomsma, Dorret I

Published
2020

49. Out of Control: Examining the Association Between Family Conflict and Self-Control in Adolescence in a Genetically Sensitive Design

Author

Leerstoel Finkenauer, Youth in Changing Cultural Contexts, Willems, Yayouk E, de Zeeuw, Eveline L, van Beijsterveldt, Catharina E M, Boomsma, Dorret I, Bartels, Meike, Finkenauer, Catrin, Leerstoel Finkenauer, Youth in Changing Cultural Contexts, Willems, Yayouk E, de Zeeuw, Eveline L, van Beijsterveldt, Catharina E M, Boomsma, Dorret I, Bartels, Meike, and Finkenauer, Catrin

Published
2020

50. Harmonizing behavioral outcomes across studies, raters, and countries: application to the genetic analysis of aggression in the ACTION Consortium

Author

Luningham, Justin M, Hendriks, Anne M, Krapohl, Eva, Fung Ip, Hill, van Beijsterveldt, Catharina E M, Lundström, Sebastian, Vuoksimaa, Eero, Korhonen, Tellervo, Lichtenstein, Paul, Plomin, Robert, Pulkkinen, Lea, Rose, Richard J, Kaprio, Jaakko, Bartels, Meike, Boomsma, Dorret I, Lubke, Gitta H, Luningham, Justin M, Hendriks, Anne M, Krapohl, Eva, Fung Ip, Hill, van Beijsterveldt, Catharina E M, Lundström, Sebastian, Vuoksimaa, Eero, Korhonen, Tellervo, Lichtenstein, Paul, Plomin, Robert, Pulkkinen, Lea, Rose, Richard J, Kaprio, Jaakko, Bartels, Meike, Boomsma, Dorret I, and Lubke, Gitta H

Abstract

BACKGROUND: Aggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school-aged children to jointly analyze data from five large twin cohorts.METHODS: Individual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model-based phenotype harmonization approach. A bi-factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sample size allowed adequate power to test for sibling interaction effects, with unique dynamics permitted for opposite-sex twins.RESULTS: The best-fitting model found a high level of overall heritability of aggression (~60%). Different heritability rates of aggression across sex were marginally significant, with heritability estimates in boys of ~64% and ~58% in girls. Sibling interaction effects were only significant in the opposite-sex twin pairs: the interaction effect of males on their female co-twin differed from the effect of females on their male co-twin. An aggressive female had a positive effect on male co-twin aggression, whereas more aggression in males had a negative influence on a female co-twin.CONCLUSIONS: Opposite-sex twins displayed unique social dynamics of aggressive behaviors in a joint analysis of a large, multinational dataset. The integrative data analysis framework, applied in combination with a reference panel, has the potential to elucid

Published
2020
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