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Gene–environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding
- Boris Klingenberg, Sinan Guloksuz, Lotta-Katrin Pries, Ozan Cinar, Claudia Menne-Lothmann, Jeroen Decoster, Ruud van Winkel, Dina Collip, Philippe Delespaul, Marc De Hert, Catherine Derom, Evert Thiery, Nele Jacobs, Marieke Wichers, Bochao D. Lin, Jurjen Luykx, Jim van Os, Bart P. F. Rutten
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- Journal:
- Personality Neuroscience / Volume 6 / 2023
- Published online by Cambridge University Press:
- 04 August 2023, e5
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The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRSN), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic and 436 dizygotic twins and 319 twin pairs. The Short Eysenck Personality questionnaire was used to measure neuroticism. PRSN was trained on the results from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB) cohorts, yielding two different PRSN. Multilevel mixed-effects models were used to analyze the main and interacting associations of PRSN, childhood adversity, bullying, and parental bonding style with neuroticism. We found no evidence of gene–environment correlation. PRSN thresholds of .005 and .2 were chosen, based on GPC and UKB datasets, respectively. After correction for confounders, all the individual variables were associated with the expression of neuroticism: both PRSN from GPC and UKB, childhood adversity, maternal bonding, paternal bonding, and bullying in primary school and secondary school. However, the results indicated no evidence for gene–environment interaction in this cohort. These results suggest that genetic vulnerability on the one hand and negative life events (childhood adversity and bullying) and positive life events (optimal parental bonding) on the other represent noninteracting pathways to neuroticism.
Affective wellbeing moderates the association between polygenic risk score for neuroticism and change in neuroticism
- J. Bahbouhová, M. V. Cade, A. T. De Sadeleer, C. Dibbets, L.-Q. Herrmann, P. O. F. Hovens, B. M. Jakson, R. C. Reising, C. Menne-Lothmann, J. Decoster, R. van Winkel, D. Collip, P. Delespaul, M. De Hert, C. Derom, E. Thiery, N. Jacobs, M. Wichers, J. van Os, B. P. F. Rutten, S. Gülöksüz, B. Klingenberg
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S175
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Introduction
Neuroticism has societal, mental and physical health relevance, with an etiology involving genetic predisposition, psychological influence, and their interaction.
ObjectivesTo understand whether the association between polygenic risk score for neuroticism (PRS-N) and neuroticism is moderated by affective well-being.
MethodsData were derived from TwinssCan, a general population twin cohort (age range=15-35 years, 478 monozygotic twins). Self-report questionnaires were used to measure well-being and neuroticism. PRS-N was trained from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB). Multilevel mixed-effects models were used to test baseline and changes in well-being and neuroticism.
ResultsBaseline wellbeing and neuroticism were associated (β=-1.35, p<0.001). PRSs-N were associated with baseline neuroticism (lowest p-value: 0.008 in GPC, 0.01 in UKB). In interaction models (PRS x wellbeing), GPC PRS-N (β=0.38, p=0.04) and UKB PRS-N (β=0.81, p<0.001) had significant interactions.
PRSs-N were associated with changes in neuroticism (lowest p-value: 0.03 in GPC, 0.3 in UKB). Furthermore, changes in wellbeing and neuroticism were associated (β =-0.66, p<0.001). In interaction models (PRS x change in wellbeing), only UKB PRS-N had a significant interaction (β=0.80, p<0.001).
ConclusionsInteraction between polygenic risk, wellbeing and neuroticism, were observed regarding baselines measures and change over time. Depending on the analysis step, the direction of the effect changed.
Disclosure of InterestNone Declared
Differential associations of childhood adversity subtypes and psychopathology in men and women
- T. Prachason, I. Mutlu, L. Fusar-Poli, C. Menne-Lothmann, J. Decoster, R. van Winkel, D. Collip, P. Delespaul, M. De Hert, C. Derom, E. Thiery, N. Jacobs, M. Wichers, J. van Os, B. P. F. Rutten, L.-K. Pries, S. Gülöksüz
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S80-S81
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Introduction
Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA subtypes and psychiatric symptoms is limited.
ObjectivesTo test the gender-specific associations of CA subtypes and psychiatric symptoms in the general population.
MethodsData from 791 twins and siblings from the TwinssCan project were used. Psychopathology and CA exposure were assessed using the Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire (CTQ), respectively. The associations between the total CTQ scores and SCL-90 scores (i.e. total SCL-90, psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety) were tested in men and women separately. The associations between the five CA subtypes (i.e. physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and total SCL-90 were tested in a mutually adjusted model. As exploratory analyses, the associations between all CA subtypes and the nine SCL-90 subdomain scores were similarly tested. The regression coefficients between men and women were compared using Chow’s test. All models were adjusted for age and family structure.
ResultsTotal CTQ was significantly associated with total SCL-90 in men (B = 0.013, SE = 0.003, P < .001) and women (B = 0.011, SE = 0.002, P < .001). The associations with the nine symptom domains were also significant in both genders (P < .001). No significant gender differences in the regression coefficients of total CTQ were detected. The analyses of CA subtypes showed a significant association between emotional abuse and total SCL-90 in women (B = 0.173, SE = 0.030, P < .001) and men (B = 0.080, SE = 0.035, P = .023), but the association was significantly stronger in women (ꭓ2(1) = 4.10, P = .043). The association of sexual abuse and total SCL-90 was only significant in women (B = 0.217, SE = 0.053, P < .001). The associations of emotional neglect (B = 0.061, SE = 0.027, P = .026) and physical neglect (B = 0.167, SE = 0.043, P < .001) with total SCL-90 were only significant in men. The explorative analyses of SCL-90 subdomains revealed significant associations of emotional abuse with all nine symptom domains and of sexual abuse with seven symptom domains in women. Significant associations of physical neglect with six symptom domains and of emotional neglect with depression were also detected in men. No other significant associations between CT subtypes and total SCL-90 or symptom domain scores were observed in men and women.
ConclusionsCA exposure was associated with diverse psychopathology similarly in both genders. However, women are more sensitive to abuse, but men are more sensitive to neglect. Gender-specific influences of CA subtypes on psychopathology should be considered in future studies.
Disclosure of InterestNone Declared
The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- K. Silventoinen, A. Jelenkovic, Y. Yokoyama, R. Sund, M. Sugawara, M. Tanaka, S. Matsumoto, L. H. Bogl, D. L. Freitas, J. A. Maia, J. v. B. Hjelmborg, S. Aaltonen, M. Piirtola, A. Latvala, L. Calais-Ferreira, V. C. Oliveira, P. H. Ferreira, F. Ji, F. Ning, Z. Pang, J. R. Ordoñana, J. F. Sánchez-Romera, L. Colodro-Conde, S. A. Burt, K. L. Klump, N. G. Martin, S. E. Medland, G. W. Montgomery, C. Kandler, T. A. McAdams, T. C. Eley, A. M. Gregory, K. J. Saudino, L. Dubois, M. Boivin, M. Brendgen, G. Dionne, F. Vitaro, A. D. Tarnoki, D. L. Tarnoki, C. M. A. Haworth, R. Plomin, S. Y. Öncel, F. Aliev, E. Medda, L. Nisticò, V. Toccaceli, J. M. Craig, R. Saffery, S. H. Siribaddana, M. Hotopf, A. Sumathipala, F. Rijsdijk, H.-U. Jeong, T. Spector, M. Mangino, G. Lachance, M. Gatz, D. A. Butler, W. Gao, C. Yu, L. Li, G. Bayasgalan, D. Narandalai, K. P. Harden, E. M. Tucker-Drob, K. Christensen, A. Skytthe, K. O. Kyvik, C. A. Derom, R. F. Vlietinck, R. J. F. Loos, W. Cozen, A. E. Hwang, T. M. Mack, M. He, X. Ding, J. L. Silberg, H. H. Maes, T. L. Cutler, J. L. Hopper, P. K. E. Magnusson, N. L. Pedersen, A. K. Dahl Aslan, L. A. Baker, C. Tuvblad, M. Bjerregaard-Andersen, H. Beck-Nielsen, M. Sodemann, V. Ullemar, C. Almqvist, Q. Tan, D. Zhang, G. E. Swan, R. Krasnow, K. L. Jang, A. Knafo-Noam, D. Mankuta, L. Abramson, P. Lichtenstein, R. F. Krueger, M. McGue, S. Pahlen, P. Tynelius, F. Rasmussen, G. E. Duncan, D. Buchwald, R. P. Corley, B. M. Huibregtse, T. L. Nelson, K. E. Whitfield, C. E. Franz, W. S. Kremen, M. J. Lyons, S. Ooki, I. Brandt, T. S. Nilsen, J. R. Harris, J. Sung, H. A. Park, J. Lee, S. J. Lee, G. Willemsen, M. Bartels, C. E. M. van Beijsterveldt, C. H. Llewellyn, A. Fisher, E. Rebato, A. Busjahn, R. Tomizawa, F. Inui, M. Watanabe, C. Honda, N. Sakai, Y.-M. Hur, T. I. A. Sørensen, D. I. Boomsma, J. Kaprio
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- Twin Research and Human Genetics / Volume 22 / Issue 6 / December 2019
- Published online by Cambridge University Press:
- 31 July 2019, pp. 800-808
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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Sprays from droplets impacting a mesh
- S. A. Kooij, A. M. Moqaddam, T. C. de Goede, D. Derome, J. Carmeliet, N. Shahidzadeh, D. Bonn
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- Journal of Fluid Mechanics / Volume 871 / 25 July 2019
- Published online by Cambridge University Press:
- 22 May 2019, pp. 489-509
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In liquid spray applications, the sprays are often created by the formation and destabilization of a liquid sheet or jet. The disadvantage of such atomization processes is that the breakup is often highly irregular, causing a broad distribution of droplet sizes. As these sizes are controlled by the ligament corrugation and size, a monodisperse spray should consist of ligaments that are both smooth and of equal size. A straightforward way of creating smooth and equally sized ligaments is by droplet impact on a mesh. In this work we show that this approach does however not produce monodisperse droplets, but instead the droplet size distribution is very broad, with a large number of small satellite drops. We demonstrate that the fragmentation is controlled by a jet instability, where initial perturbations caused by the injection process result in long-wavelength disturbances that determine the final ligament breakup. During destabilization the crests of these disturbances are connected by thin ligaments which are the leading cause of the large number of small droplets. A secondary coalescence process, due to small relative velocities between droplets, partly masks this effect by reducing the amount of small droplets. Of the many parameters in this system, we describe the effect of varying the mesh size, mesh rigidity, impact velocity and wetting properties, keeping the liquid properties the same by focusing on water droplets only. We further perform lattice Boltzmann modelling of the impact process that reproduces key features seen in the experimental data.
Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts
- Karri Silventoinen, Aline Jelenkovic, Antti Latvala, Reijo Sund, Yoshie Yokoyama, Vilhelmina Ullemar, Catarina Almqvist, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Christian Kandler, Chika Honda, Fujio Inui, Yoshinori Iwatani, Mikio Watanabe, Esther Rebato, Maria A. Stazi, Corrado Fagnani, Sonia Brescianini, Yoon-Mi Hur, Hoe-Uk Jeong, Tessa L. Cutler, John L. Hopper, Andreas Busjahn, Kimberly J. Saudino, Fuling Ji, Feng Ning, Zengchang Pang, Richard J. Rose, Markku Koskenvuo, Kauko Heikkilä, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Joohon Sung, Jina Kim, Jooyeon Lee, Sooji Lee, Tracy L. Nelson, Keith E. Whitfield, Qihua Tan, Dongfeng Zhang, Clare H. Llewellyn, Abigail Fisher, S. Alexandra Burt, Kelly L. Klump, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Sarah E. Medland, Nicholas G. Martin, Grant W. Montgomery, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Robin P. Corley, Brooke M. Huibregtse, Sevgi Y. Öncel, Fazil Aliev, Robert F. Krueger, Matt McGue, Shandell Pahlen, Gonneke Willemsen, Meike Bartels, Catharina E. M. van Beijsterveldt, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Jennifer R. Harris, Ingunn Brandt, Thomas S. Nilsen, Finn Rasmussen, Per Tynelius, Laura A. Baker, Catherine Tuvblad, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, Margaret Gatz, David A. Butler, Paul Lichtenstein, Jack H. Goldberg, K. Paige Harden, Elliot M. Tucker-Drob, Glen E. Duncan, Dedra Buchwald, Adam D. Tarnoki, David L. Tarnoki, Carol E. Franz, William S. Kremen, Michael J. Lyons, José A. Maia, Duarte L. Freitas, Eric Turkheimer, Thorkild I. A. Sørensen, Dorret I. Boomsma, Jaakko Kaprio
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- Twin Research and Human Genetics / Volume 20 / Issue 5 / October 2017
- Published online by Cambridge University Press:
- 04 October 2017, pp. 395-405
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Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Universal rescaling of drop impact on smooth and rough surfaces
- J. B. Lee, N. Laan, K. G. de Bruin, G. Skantzaris, N. Shahidzadeh, D. Derome, J. Carmeliet, D. Bonn
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- Journal of Fluid Mechanics / Volume 786 / 10 January 2016
- Published online by Cambridge University Press:
- 30 November 2015, R4
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The maximum spreading of drops impacting on smooth and rough surfaces is measured from low to high impact velocity for liquids with different surface tensions and viscosities. We demonstrate that dynamic wetting plays an important role in the spreading at low velocity, characterized by the dynamic contact angle at maximum spreading. In the energy balance, we account for the dynamic wettability by introducing the capillary energy at zero impact velocity, which relates to the spreading ratio at zero impact velocity. Correcting the measured spreading ratio by the spreading ratio at zero velocity, we find a correct scaling behaviour for low and high impact velocity and, by interpolation between the two, we find a universal scaling curve. The influence of the liquid as well as the nature and roughness of the surface are taken into account properly by rescaling with the spreading ratio at zero velocity, which, as demonstrated, is equivalent to accounting for the dynamic contact angle.
Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project
- Aline Jelenkovic, Yoshie Yokoyama, Reijo Sund, Chika Honda, Leonie H Bogl, Sari Aaltonen, Fuling Ji, Feng Ning, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Adam D. Tarnoki, David L. Tarnoki, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Bia Kim, Youngsook Chong, Changhee Hong, Hyun Jung Shin, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Finn Rasmussen, Yoon-Mi Hur, Dorret I. Boomsma, Thorkild I. A. Sørensen, Jaakko Kaprio, Karri Silventoinen
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- Twin Research and Human Genetics / Volume 18 / Issue 5 / October 2015
- Published online by Cambridge University Press:
- 04 September 2015, pp. 557-570
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A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- Karri Silventoinen, Aline Jelenkovic, Reijo Sund, Chika Honda, Sari Aaltonen, Yoshie Yokoyama, Adam D. Tarnoki, David L. Tarnoki, Feng Ning, Fuling Ji, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L. Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Changhee Hong, Youngsook Chong, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Finn Rasmussen, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Dorret I. Boomsma, Yoon-Mi Hur, Thorkild I. A. Sørensen, Jaakko Kaprio
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- Twin Research and Human Genetics / Volume 18 / Issue 4 / August 2015
- Published online by Cambridge University Press:
- 27 May 2015, pp. 348-360
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For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Twin-Specific Intrauterine ‘Growth’ Charts Based on Cross-Sectional Birthweight Data
- Marij Gielen, Patrick J. Lindsey, Catherine Derom, Ruth J. F. Loos, Nicole Y. Souren, Aimee D. C. Paulussen, Maurice P. Zeegers, Robert Derom, Robert Vlietinck, Jan G. Nijhuis
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- Twin Research and Human Genetics / Volume 11 / Issue 2 / 01 April 2008
- Published online by Cambridge University Press:
- 21 February 2012, pp. 224-235
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The assessment of fetal growth is an essential component of good antenatal care, especially for twins. The aims of this study are to develop twin-specific intrauterine 'growth' charts, based on cross-sectional birthweight data, for monochorionic and dichorionic twins according to sex and parity, and to detect twins at risk for neonatal death by comparing the use of twin-specific and singleton charts. The study sample consisted of 76,471 singletons and 8454 twins (4227 pairs) born in East Flanders (Belgium). Birthweights were analyzed using a nonlinear Gaussian regression. After 33 weeks of gestation, the birthweights of twins started to deviate from singletons (difference of 900 grams at 42 weeks). Birthweights of dichorionic twins continued to increase, whereas those of monochorionic twins decreased after week 40 (difference of more than 300 g at 42 weeks). After 31 weeks of gestation, neonatal mortality increased as centile decreased, and was especially high if birthweight was below the twin-specific third centile: .032 (below) versus .007 (above). Using singleton centiles, this was less obvious. In conclusion, twin-specific growth charts, taking chorionicity into account, are more accurate to detect twins at risk for neonatal death. Therefore the presented charts, based on cross-sectional birthweight data, enable an improved assessment of twin growth.
Anthropometry, Carbohydrate and Lipid Metabolism in the East Flanders Prospective Twin Survey: Linkage of Candidate Genes Using Two Sib-Pair Based Variance Components Analyses
- Nicole Y. Souren, Maurice P. Zeegers, Rob G. J. H. Janssen, Anja Steyls, Marij Gielen, Ruth J. F. Loos, Gaston Beunen, Robert Fagard, Alphons P. M. Stassen, Jeroen Aerssens, Catherine Derom, Robert Vlietinck, Aimee D. C. Paulussen
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- Twin Research and Human Genetics / Volume 11 / Issue 5 / 01 October 2008
- Published online by Cambridge University Press:
- 21 February 2012, pp. 505-516
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Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.
Life events and borderline personality features: the influence of gene–environment interaction and gene–environment correlation
- M. A. Distel, C. M. Middeldorp, T. J. Trull, C. A. Derom, G. Willemsen, D. I. Boomsma
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- Journal:
- Psychological Medicine / Volume 41 / Issue 4 / April 2011
- Published online by Cambridge University Press:
- 01 July 2010, pp. 849-860
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Background
Traumatic life events are generally more common in patients with borderline personality disorder (BPD) than in non-patients or patients with other personality disorders. This study investigates whether exposure to life events moderates the genetic architecture of BPD features. As the presence of genotype–environment correlation (rGE) can lead to spurious findings of genotype–environment interaction (G×E), we also test whether BPD features increase the likelihood of exposure to life events.
MethodThe extent to which an individual is at risk to develop BPD was assessed with the Personality Assessment Inventory – Borderline features scale (PAI-BOR). Life events under study were a divorce/break-up, traffic accident, violent assault, sexual assault, robbery and job loss. Data were available for 5083 twins and 1285 non-twin siblings. Gene–environment interaction and correlation were assessed by using structural equation modelling (SEM) and the co-twin control design.
ResultsThere was evidence for both gene–environment interaction and correlation. Additive genetic influences on BPD features interacted with the exposure to sexual assault, with genetic variance being lower in exposed individuals. In individuals who had experienced a divorce/break-up, violent assault, sexual assault or job loss, environmental variance for BPD features was higher, leading to a lower heritability of BPD features in exposed individuals. Gene–environment correlation was present for some life events. The genes that influence BPD features thus also increased the likelihood of being exposed to certain life events.
ConclusionsTo our knowledge, this study is the first to test the joint effect of genetic and environmental influences and the exposure to life events on BPD features in the general population. Our results indicate the importance of both genetic vulnerability and life events.
Mechanisms of gene–environment interactions in depression: evidence that genes potentiate multiple sources of adversity
- M. Wichers, D. Schrijvers, N. Geschwind, N. Jacobs, I. Myin-Germeys, E. Thiery, C. Derom, B. Sabbe, F. Peeters, Ph. Delespaul, J. van Os
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- Psychological Medicine / Volume 39 / Issue 7 / July 2009
- Published online by Cambridge University Press:
- 06 October 2008, pp. 1077-1086
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Background
Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity.
MethodTwin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA.
ResultsAll three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity.
ConclusionsThe findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.
Heritability of borderline personality disorder features is similar across three countries
- M. A. Distel, T. J. Trull, C. A. Derom, E. W. Thiery, M. A. Grimmer, N. G. Martin, G. Willemsen, D. I. Boomsma
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- Psychological Medicine / Volume 38 / Issue 9 / September 2008
- Published online by Cambridge University Press:
- 08 November 2007, pp. 1219-1229
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Background
Most of our knowledge about borderline personality disorder features has been obtained through the study of clinical samples. Although these studies are important in their own right, they are limited in their ability to address certain important epidemiological and aetiological questions such as the degree to which there is a genetic influence on the manifestation of borderline personality disorder features. Though family history studies of borderline personality disorder indicate genetic influences, there have been very few twin studies and the degree of genetic influence on borderline personality disorder remains unclear.
MethodData were drawn from twin samples from The Netherlands (n=3918), Belgium (n=904) and Australia (n=674). In total, data were available on 5496 twins between the ages of 18 and 86 years from 3644 families who participated in the study by completion of a mailed self-report questionnaire on borderline personality disorder features.
ResultsIn all countries, females scored higher than males and there was a general tendency for younger adults to endorse more borderline personality disorder features than older adults. Model-fitting results showed that additive genetic influences explain 42% of the variation in borderline personality disorder features in both men and women and that this heritability estimate is similar across The Netherlands, Belgium and Australia. Unique environmental influences explain the remaining 58% of the variance.
ConclusionGenetic factors play a role in individual differences in borderline personality disorder features in Western society.