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The Concept of Resistance to Substance Use and a Research Approach: The Resist! Project
- Michael M. Vanyukov, Hermine H. M. Maes, William G. Iacono, Levent Kirisci, Diana R. Samek, Judy L. Silberg, Emily B. Zimmerman, Elizabeth C. Prom-Wormley
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- Twin Research and Human Genetics / Volume 26 / Issue 1 / February 2023
- Published online by Cambridge University Press:
- 10 March 2023, pp. 31-39
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Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.
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.
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.
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.
Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood
- Daniel E. Adkins, Shaunna L. Clark, William E. Copeland, Martin Kennedy, Kevin Conway, Adrian Angold, Hermine Maes, Youfang Liu, Gaurav Kumar, Alaattin Erkanli, Ashwin A. Patkar, Judy Silberg, Tyson H. Brown, David M. Fergusson, L. John Horwood, Lindon Eaves, Edwin J. C. G. van den Oord, Patrick F. Sullivan, E. J. Costello
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- Twin Research and Human Genetics / Volume 18 / Issue 4 / August 2015
- Published online by Cambridge University Press:
- 17 June 2015, pp. 335-347
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The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
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.
Risk Factors Influencing Smoking Behavior: A Turkish Twin Study
- Sevgi Yurt Öncel, Danielle M. Dick, Hermine H. Maes, Fazil Alıev
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- Twin Research and Human Genetics / Volume 17 / Issue 6 / December 2014
- Published online by Cambridge University Press:
- 24 July 2014, pp. 563-573
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Aim: In this study, we introduce the first twin study in Turkey, focusing on smoking behavior, and laying the foundation to register all twins born in Turkey for research purposes. Using Turkish twins will contribute to our understanding of health problems in the context of cultural differences. Materials and methods: We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey, and administered a health and lifestyle interview that included questions about smoking status and smoking history. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit bivariate Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to smoking outcomes in this sample. Results: One hundred seventy-eight participants (28.8%) were identified as smokers, smoking every day for a month or longer, of whom 79.2% were males and 20.8% were females. Mean values for number of cigarettes per day and the Fagerstrom Test of Nicotine Dependence (FTND; Fagerstrom, 1978) score were higher in males than in females, and age of onset was earlier in males. There was a significant positive correlation between the FTND score and number of cigarettes smoked per day, and a significant negative correlation between both variables and age at onset of smoking. Our study showed that gender, presence of a smoking twin in the family, age, alcohol use, marital status, daily sports activities, and feeling moody all played a significant role in smoking behavior among twins. The twin analysis suggested that 79.5% of the liability to FTND was influenced by genetic factors and 20.5% by unique environment, while familial resemblance for smoking initiation was best explained by common environmental factors. Conclusions: Marked differences in the prevalence of smoking behavior in men versus women were observed for the Turkish population. Genetic analyses showed that common environmental factors primarily contributed to smoking initiation, while genetic factors explained a greater proportion of variance in liability to nicotine dependence. Our study shows higher heritability estimate of the FTND scores and higher shared environmental influence on smoking initiation for both males and females than reported in previous studies.
Modeling Extended Twin Family Data I: Description of the Cascade Model
- Matthew C. Keller, Sarah E. Medland, Laramie E. Duncan, Peter K. Hatemi, Michael C. Neale, Hermine H. M. Maes, Lindon J. Eaves
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- Twin Research and Human Genetics / Volume 12 / Issue 1 / 01 February 2009
- Published online by Cambridge University Press:
- 21 February 2012, pp. 8-18
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The classical twin design uses data on the variation of and covariation between monozygotic and dizygotic twins to infer underlying genetic and environmental causes of phenotypic variation in the population. By using data from additional relative classes, such as parents, extended twin family designs more comprehensively describe the causes of phenotypic variation. This article introduces an extension of previous extended twin family models, the Cascade model, which uses information on twins as well as their siblings, spouses, parents, and children to differentiate two genetic and six environmental sources of phenotypic variation. The Cascade also relaxes assumptions regarding mating and cultural transmission that existed in previous extended twin family designs. The estimation of additional parameters and relaxation of assumptions is potentially important, not only because it allows more fine-grained descriptions of the causes of phenotypic variation, but more importantly, because it can reduce the biases in parameter estimates that exist in earlier designs.
Adolescent religiousness and its influence on substance use: preliminary findings from the Mid-Atlantic School Age Twin Study
- Brian M D'Onofrio, Lenn Murrelle, Lindon J Eaves, Michael E McCullough, Jessica L Landis, Hermine H Maes
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- Twin Research / Volume 2 / Issue 2 / 01 April 1999
- Published online by Cambridge University Press:
- 21 February 2012, pp. 156-168
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Research has consistently shown that religiousness is associated with lower levels of alcohol and drug use, but little is known about the nature of adolescent religiousness or the mechanisms through which it influences problem behavior in this age group. This paper presents preliminary results from the Mid-Atlantic School Age Twin Study, a prospective, population-based study of 6–18-year-old twins and their mothers. Factor analysis of a scale developed to characterize adolescent religiousness, the Religious Attitudes and Practices Inventory (RAPI), revealed three factors: theism, religious/spiritual practices, and peer religiousness. Twin correlations and univariate behavior-genetic models for these factors and a measure of belief that drug use is sinful reveal in 357 twin pairs that common environmental factors significantly influence these traits, but a minor influence of genetic factors could not be discounted. Correlations between the multiple factors of adolescent religiousness and substance use, comorbid problem behavior, mood disorders, and selected risk factors for substance involvement are also presented. Structural equation modeling illustrates that specific religious beliefs about the sinfulness of drugs and level of peer religiousness mediate the relationship between theistic beliefs and religious/spiritual practices on substance use. Limitations and future analyses are discussed.
A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence
- HERMINE H. MAES, PATRICK F. SULLIVAN, CYNTHIA M. BULIK, MICHAEL C. NEALE, CAROL A. PRESCOTT, LINDON J. EAVES, KENNETH S. KENDLER
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- Psychological Medicine / Volume 34 / Issue 7 / October 2004
- Published online by Cambridge University Press:
- 21 October 2004, pp. 1251-1261
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Background. Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary.
Method. We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry.
Results. The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80% of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75%, 80% and 60% respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females.
Conclusions. This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.