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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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- Journal:
- 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.
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
- Renato Polimanti, Roseann E. Peterson, Jue-Sheng Ong, Stuart MacGregor, Alexis C. Edwards, Toni-Kim Clarke, Josef Frank, Zachary Gerring, Nathan A. Gillespie, Penelope A. Lind, Hermine H. Maes, Nicholas G. Martin, Hamdi Mbarek, Sarah E. Medland, Fabian Streit, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Arpana Agrawal, Howard J. Edenberg, Kenneth S. Kendler, Cathryn M. Lewis, Patrick F. Sullivan, Naomi R. Wray, Joel Gelernter, Eske M. Derks
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- Psychological Medicine / Volume 49 / Issue 7 / May 2019
- Published online by Cambridge University Press:
- 01 April 2019, pp. 1218-1226
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Background
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
MethodsLinkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
ResultsPositive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
ConclusionThis study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Social Competence in Parents Increases Children’s Educational Attainment: Replicable Genetically-Mediated Effects of Parenting Revealed by Non-Transmitted DNA
- Timothy C. Bates, Brion S. Maher, Lucía Colodro-Conde, Sarah E. Medland, Kerrie McAloney, Margaret J. Wright, Narelle K. Hansell, Aysu Okbay, Kenneth S. Kendler, Nicholas G. Martin, Nathan A. Gillespie
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- Journal:
- Twin Research and Human Genetics / Volume 22 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 21 January 2019, pp. 1-3
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We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.
Significant concordance of genetic variation that increases both the risk for obsessive–compulsive disorder and the volumes of the nucleus accumbens and putamen
- Derrek P. Hibar, Joshua W. Cheung, Sarah E. Medland, Mary S. Mufford, Neda Jahanshad, Shareefa Dalvie, Raj Ramesar, Evelyn Stewart, Odile A. van den Heuvel, David L. Pauls, James A. Knowles, Dan J. Stein, Paul M. Thompson, Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA) Consortium and International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC)
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- Journal:
- The British Journal of Psychiatry / Volume 213 / Issue 1 / July 2018
- Published online by Cambridge University Press:
- 27 June 2018, pp. 430-436
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- July 2018
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Background
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
AimsWe present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
MethodUsing single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
ResultsWe found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
ConclusionsThese results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interestThe authors have declared that no competing interests exist.
The Nature of Nurture: Using a Virtual-Parent Design to Test Parenting Effects on Children's Educational Attainment in Genotyped Families
- Timothy C. Bates, Brion S. Maher, Sarah E. Medland, Kerrie McAloney, Margaret J. Wright, Narelle K. Hansell, Kenneth S. Kendler, Nicholas G. Martin, Nathan A. Gillespie
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- Twin Research and Human Genetics / Volume 21 / Issue 2 / April 2018
- Published online by Cambridge University Press:
- 13 March 2018, pp. 73-83
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Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
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.
Obstetrical, pregnancy and socio-economic predictors for new-onset severe postpartum psychiatric disorders in primiparous women
- S. Meltzer-Brody, M. L. Maegbaek, S. E. Medland, W. C. Miller, P. Sullivan, T. Munk-Olsen
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- Psychological Medicine / Volume 47 / Issue 8 / June 2017
- Published online by Cambridge University Press:
- 23 January 2017, pp. 1427-1441
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Background
Childbirth is a potent trigger for the onset of psychiatric illness in women including postpartum depression (PPD) and postpartum psychosis (PP). Medical complications occurring during pregnancy and/or childbirth have been linked to postpartum psychiatric illness and sociodemographic factors. We evaluated if pregnancy and obstetrical predictors have similar effects on different types of postpartum psychiatric disorders.
MethodA population-based cohort study using Danish registers was conducted in 392 458 primiparous women with a singleton delivery between 1995 and 2012 and no previous psychiatric history. The main outcome was first-onset postpartum psychiatric episodes. Incidence rate ratios (IRRs) were calculated for any psychiatric contact in four quarters for the first year postpartum.
ResultsPPD and postpartum acute stress reactions were associated with pregnancy and obstetrical complications. For PPD, hyperemesis gravidarum [IRR 2.69, 95% confidence interval (CI) 1.93–3.73], gestational hypertension (IRR 1.84, 95% CI 1.33–2.55), pre-eclampsia (IRR 1.45, 95% CI 1.14–1.84) and Cesarean section (C-section) (IRR 1.32, 95% CI 1.13–1.53) were associated with increased risk. For postpartum acute stress, hyperemesis gravidarum (IRR 1.93, 95% CI 1.38–2.71), preterm birth (IRR 1.51, 95% CI 1.30–1.75), gestational diabetes (IRR 1.42, 95% CI 1.03–1.97) and C-section (IRR 1.36, 95% CI 1.20–1.55) were associated with increased risk. In contrast, risk of PP was not associated with pregnancy or obstetrical complications.
ConclusionsPregnancy and obstetrical complications can increase the risk for PPD and acute stress reactions but not PP. Identification of postpartum women requiring secondary care is needed to develop targeted approaches for screening and treatment. Future work should focus on understanding the contributions of psychological stressors and underlying biology on the development of postpartum psychiatric illness.
Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project
- Yoshie Yokoyama, Aline Jelenkovic, Reijo Sund, Joohon Sung, John L. Hopper, Syuichi Ooki, Kauko Heikkilä, Sari Aaltonen, Adam D. Tarnoki, David L. Tarnoki, Gonneke Willemsen, Meike Bartels, Toos C. E. M. van Beijsterveldt, Kimberly J. Saudino, Tessa L. Cutler, Tracy L. Nelson, Keith E. Whitfield, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Mingguang He, Xiaohu Ding, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Yun-Mi Song, Sarah Yang, Kayoung Lee, Hoe-Uk Jeong, Ariel Knafo-Noam, David Mankuta, Lior Abramson, S. Alexandra Burt, Kelly L. Klump, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, Jennifer R. Harris, Ingunn Brandt, Thomas Sevenius Nilsen, Jeffrey M. Craig, Richard Saffery, Fuling Ji, Feng Ning, Zengchang Pang, Lise Dubois, Michel Boivin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Nicholas G. Martin, Sarah E. Medland, Grant W. Montgomery, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Per Tynelius, Claire M. A. Haworth, Robert Plomin, Esther Rebato, Richard J. Rose, Jack H. Goldberg, Finn Rasmussen, Yoon-Mi Hur, Thorkild I. A. Sørensen, Dorret I. Boomsma, Jaakko Kaprio, Karri Silventoinen
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- Twin Research and Human Genetics / Volume 19 / Issue 2 / April 2016
- Published online by Cambridge University Press:
- 09 March 2016, pp. 112-124
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We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
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.
A Longitudinal Genetic Study of Uric Acid and Liver Enzymes in Adolescent Twins
- Rita P. S. Middelberg, Sarah E. Medland, Nicholas G. Martin, John B. Whitfield
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- Twin Research and Human Genetics / Volume 10 / Issue 5 / 01 October 2007
- Published online by Cambridge University Press:
- 21 February 2012, pp. 757-764
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Biochemical traits such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and uric acid are associated with obesity, and with risk of cardiovascular disease, metabolic syndrome and diabetes. Each is subject to genetic influences, but little is known about changes in genetic and environmental influences on these traits over time. We investigated the contribution of genetic and environmental influences to variation in these biochemical traits in adolescent twins and their nontwin siblings from 965 twin families. Twins were studied at ages 12, 14 and 16 years. Multivariate genetic models that included effects of age and sex were fitted to determine whether the same or different genetic or environmental factors influence each trait at different ages. Results showed that the genetic factors influencing AST, ALT, GGT and uric acid change over time during adolescence, and that the magnitude of these effects differs between males and females. The nonshared environment effects were generally time specific. There are developmental changes in genes affecting these traits during adolescence.
Genetic co-morbidity between neuroticism, anxiety/depression and somatic distress in a population sample of adolescent and young adult twins
- N. K. Hansell, M. J. Wright, S. E. Medland, T. A. Davenport, N. R. Wray, N. G. Martin, I. B. Hickie
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- Psychological Medicine / Volume 42 / Issue 6 / June 2012
- Published online by Cambridge University Press:
- 04 November 2011, pp. 1249-1260
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Background
Genetic studies in adults indicate that genes influencing the personality trait of neuroticism account for substantial genetic variance in anxiety and depression and in somatic health. Here, we examine for the first time the factors underlying the relationship between neuroticism and anxiety/depressive and somatic symptoms during adolescence.
MethodThe Somatic and Psychological Health Report (SPHERE) assessed symptoms of anxiety/depression (PSYCH-14) and somatic distress (SOMA-10) in 2459 adolescent and young adult twins [1168 complete pairs (35.4% monozygotic, 53% female)] aged 12–25 years (mean=15.5±2.9). Differences between boys and girls across adolescence were explored for neuroticism, SPHERE-34, and the subscales PSYCH-14 and SOMA-10. Trivariate analyses partitioned sources of covariance in neuroticism, PSYCH-14 and SOMA-10.
ResultsGirls scored higher than boys on both neuroticism and SPHERE, with SPHERE scores for girls increasing slightly over time, whereas scores for boys decreased or were unchanged. Neuroticism and SPHERE scores were strongly influenced by genetic factors [heritability (h2)=40–52%]. A common genetic source influenced neuroticism, PSYCH-14 and SOMA-10 (impacting PSYCH-14 more than SOMA-10). A further genetic source, independent of neuroticism, accounted for covariation specific to PSYCH-14 and SOMA-10. Environmental influences were largely specific to each measure.
ConclusionsIn adolescence, genetic risk factors indexed by neuroticism contribute substantially to anxiety/depression and, to a lesser extent, perceived somatic health. Additional genetic covariation between anxiety/depressive and somatic symptoms, independent of neuroticism, had greatest influence on somatic distress, where it was equal in influence to the factor shared with neuroticism.