Introduction to twin research for everyone: From biology to health, epigenetics, and psychology

Twin Research: Biology, Health, Epigenetics, and Psychology is a comprehensive, applied resource in twinning and twin studies that is grounded in the most impactful findings from twin research in recent years. While targeted to undergraduate and graduate students, this compendium will prove a valuable resource for scholars already familiar with twin studies, as well as those coming to the field for the first time. Here, more than forty experts across an array of disciplines examine twinning and twin research methodologies from the perspectives of biology, medicine, genetic and epigenetic influences, and neuroscience. Chapters provide clear instruction in both basic and advanced research methods, family and parenting aspects of twinning, twin studies as applied across various disease areas and medical specialties, genetic and epigenetic determinants of differentiation, and academic, neurological and cognitive development. The presentation of existing studies and methods instruction empowers students and researchers to apply twin-based research and advance new studies across a range of biomedical and behavioral fields, highlighting current research trends and future directions. Offers unique insights into twinning rates, mechanisms and factors surrounding twinship Provides clear instruction on both basic and advanced twin research methods and study design Features leading international experts in twin biology, genetics, health and psychology Examines findings from recent twin studies across a broad array of health and behavioral studies Front cover Half title Full title Copyright Contents Contributors Editor Biographies Preface Introduction to twin research for everyone: From biology to health, epigenetics, and psychology References Section 1 - Background Chapter 1 - History of Twin Studies 1.1 Twins 1.2 Twin studies 1.3 History of twin studies 1.4 Early twin studies of cognition and personality 1.5 Combining other relatives with twins 1.6 Heritability over age 1.7 Increasing sample sizes 1.8 Twin studies nowadays 1.9 Summary References Chapter 2 - Prevalence of twinning worldwide 2.1 How is that possible? One delivery and two childbirths at least 2.2 Questions of the methodology of twinning rate 2.3 Effect of assisted reproductive treatment 2.4 One out of twenty-eight births Acknowledgments References Chapter 3 - Twin family registries worldwide 3.1 Introduction 3.2 Twin family registries across the continents 3.2.1 Europe 3.2.2 North America 3.2.3 Australia 3.2.4 Asia and Middle East 3.2.5 Africa 3.2.6 Latin America and the Caribbean 3.3 International consortia 3.4 Concluding remarks References Section 2 - Phenomenon of Twinning Chapter 4 - Biology of natural twinning 4.1 Introduction 4.2 Defining factors 4.3 Conception issues 4.4 Maternal dietary factors affecting the frequency of multifetal gestations 4.5 Maternal physical factors and the rate of twinning 4.6 Biological factors tending to increase twinning 4.7 Some unique complications in twin pregnancies 4.8 Maternal risks with a twin pregnancy 4.9 Conclusions and prospectus Acknowledgments References Chapter 5 - Management and outcome of twin pregnancies 5.1 Introduction 5.2 Antenatal care 5.2.1 Diagnosis and chorionicity 5.2.2 Nutritional advice 5.2.3 Chromosomal screening: new challenges? 5.2.4 Monitoring: timing and frequency 5.2.5 Laboratory investigations 5.3 Antenatal complications 5.3.1 Chorionicity 5.3.2 Fetal growth restriction (FGR) 5.4 Specific monochorionic pregnancy complications 5.4.1 Fetal-fetal transfusion syndrome (TTTS) 5.4.2 Anemia-polycythemia sequence (TAPS) 5.4.3 Inverted arterial perfusion sequence (TRAP sequence) 5.4.4 Monoamniotic twins and cord entanglement 5.4.5 Cerebral palsy risk 5.4.6 Antenatal preventive interventions 5.5 Peripartum care 5.5.1 Timing of birth 5.5.2 Mode of delivery and induction of labor 5.6 Peri-conceptional period: a “key window” of intervention? 5.7 Conclusion References Chapter 6 - Conjoined twins 6.1 Introduction 6.2 History of conjoined twins 6.3 Conjoined status in plants and animals 6.4 Development of conjoined twins 6.5 Embryology of conjoined twins, mechanism of their development 6.6 Classification of conjoined twins 6.7 Etiology 6.8 Epidemiology of conjoined twins, genetic and demographic risk factors 6.9 Ethnicity 6.10 Summary References Section 3 - Twin Families Chapter 7 - Growing up as twins: the perspectives of twin researchers 7.1 Introduction 7.2 Adam & David Tarnoki (MZ twins or Identical Twins) 7.3 Julia Metneki (MZ twin) 7.4 Nancy L. Segal (DZ twin) 7.4.1 Personal background 7.4.2 Professional history 7.4.3 Professional activities 7.4.4 Closing statement References Chapter 8 - Parenting twins, triplets, or more 8.1 Parenting twins, triplets, or more 8.2 Pregnancy 8.3 Birth 8.4 Early months 8.5 Toddler 8.6 School years 8.7 Adolescence 8.8 Special situations 8.9 Adult twins Chapter 9 - Reared apart twins: Background, research, case studies and what they reveal about human development 9.1 Introduction 9.2 Twins raised apart: Past, present, and future 9.3 Fullerton study of Chinese twins reared apart 9.4 Unique case studies 9.5 Twin study controversy 9.6 Research directions 9.7 A quote that will endure References Chapter 10 - Opposite-sex twins in medical research 10.1 Introduction 10.2 Sharing more than a womb 10.2.1 Biological effects 10.2.2 Socialisation effects 10.3 What can sex differences in opposite-sex twin pairs tell us? 10.4 Conclusions References Section 4 - Twin Methodologies Chapter 11 - Establishing a resource for genetic, epidemiological, and biomarker studies: The important role of twin regi ... 11.1 The first steps 11.2 Strategic planning 11.3 Basic elements 11.3.1 Recruitment methods 11.3.2 Informed consent 11.3.3 Determination of zygosity in twin registries 11.3.4 Phenotyping: from survey to record linkage 11.3.5 Possibilities for biobanking in twin registers 11.3.6 Databases for twin registers 11.3.7 Data analyses issues in twin studies: batch effects and family clustering 11.3.8 Retaining the twins 11.4 Conclusion Appendix Acknowledgments Disclosure of Interests References Chapter 12 - Methodology of twin studies 12.1 Introduction 12.2 A brief note on the biometrical model 12.3 Classical twin study 12.4 Methodological assumptions 12.4.1 The equal environments assumption 12.4.2 The representativeness assumption 12.4.3 The assumption of random mating 12.5 Use of structural equation modeling in twin analysis 12.6 Analysis of discrete traits 12.6.1 Binary data 12.6.2 Threshold approaches 12.7 Extension of the classical twin model 12.8 Gene–environment correlation vs interaction 12.8.1 Genotype–environment correlation and assortative mating 12.8.2 Gene–environment interaction 12.9 Structural equation modeling for rGE and G × E interaction 12.9.1 Analysis of sex differences 12.9.2 G × E with continuous moderators 12.10 Final remarks References Chapter 13 - Twin studies of complex traits and diseases 13.1 All traits are heritable 13.2 Landmark study in twin research: MATCH 13.3 Sex differences in heritability 13.4 Are twin designs the holy grail in heritability studies? 13.5 Psychiatric disorders, comorbidity, and genetic overlap 13.6 Gene-environment interplay 13.6.1 Gene-environment correlation and gene-environment interaction 13.6.2 Gene-environment correlation (r GE) 13.6.3 Gene-environment interaction (GxE) 13.7 Mechanisms that lead to rGE and GxE 13.7.1 Cognitive ability 13.7.2 Personality 13.7.3 Externalizing behaviors 13.8 Future directions of twin studies of traits and diseases References Chapter 14 - Use of twin studies to make inference about causation for measured exposures by examining familial confounding 14.1 Introduction 14.1.1 The importance of understanding causation 14.1.2 Association is not necessarily evidence for causation 14.1.3 Proof of causation 14.1.4 A implies B does not imply B implies A 14.1.5 Bradford Hill’s so-called criteria for causation 14.1.6 Randomized controlled trials 14.1.7 Mendelian randomization 14.2 Previous twin and family study approaches to address causation 14.2.1 Within-family designs: differences versus differences 14.2.2 RCTs involving twins 14.2.3 Classic multivariate twin model (CMTM) and components of covariance 14.2.4 The direction of causation (DoC) model and the MR-DoC model 14.3 Inference about causation from examination of familial confounding (ICE FALCON) 14.3.1 Model description 14.3.2 Formal model description 14.3.3 Interpretation of changes in regression coefficients 14.3.4 Statistical inference for ICE FALCON estimates 14.4 Comparison of the CMTM, DoC model, and ICE FALCON 14.5 Applications of ICE FALCON 14.6 Further developments Funding References Chapter 15 - Twins in clinical trials 15.1 What is a randomized controlled trial? 15.2 Role of twins in RCTs 15.3 Zygosity and twin assignment across the randomized controlled trials 15.3.1 The impact of twins on sample size and power 15.3.2 Implications for future work and directions Acknowledgments References Section 5 - Behavior Chapter 16 - Twin studies in social science 16.1 Introduction 16.2 Findings from the literature 16.3 The classical twin design 16.4 Assumptions of the twin model 16.4.1 Type I error for heritability 16.4.2 Type II error for heritability 16.5 The future of twin research in the social sciences 16.6 Conclusions References Chapter 17 - Childhood development of psychiatric disorders and related traits 17.1 Introduction 17.2 Heritability of childhood psychiatric disorders and traits 17.3 Childhood psychiatric disorder and population traits have shared genetic origins 17.4 Genetic contributions to comorbidity across childhood psychiatric disorders and traits 17.5 Stability and change in the development of childhood psychiatric disorders and traits 17.6 Environmental influences on the developmental of childhood psychiatric disorders and traits 17.7 Implications & concluding remarks References Chapter 18 - Happiness and well-being: The value and findings from genetic studies 18.1 What is well-being? 18.2 Earlier reviews on twin studies on well-being 18.3 New findings of twin studies on well-being 18.4 Related phenotypes 18.4.1 Optimism 18.4.2 Meaning in life 18.4.3 Self-esteem 18.4.4 Resilience 18.4.5 Multivariate models of positive psychological traits 18.5 Specific molecular genetic and environmental influences 18.6 Future directions 18.6.1 Well-being fluctuations 18.6.2 MZ difference/causality 18.6.3 Nuclear twin family design 18.7 Conclusion References Chapter 19 - Twin study of personality 19.1 Description of personality 19.2 Twin studies of personality traits 19.3 Development trends of personality 19.4 Genetic structure of personality 19.5 Personality as a social behavior 19.6 Discordant identical twin method References Chapter 20 - Twin research in psychopathology 20.1 Schizophrenia 20.2 Depression and bipolar disorders 20.2.1 Depressive disorders 20.2.2 Bipolar disorders 20.2.3 Depression and bipolar disorder 20.3 Antisocial personality disorder (ASPD) 20.3.1 Antisocial behavior (AB) 20.3.2 Antisocial personality disorder 20.4 Implications and future directions References Chapter 21 - Cognitive aging: the role of genes and environments in patterns of change 21.1 General cognitive ability 21.2 Specific cognitive abilities 21.2.1 Age changes in genetic variance 21.2.2 Traditional cognitive domains 21.2.3 Emerging cognitive domains 21.2.4 Summary 21.3 Molecular genetics 21.3.1 Missing heritability? 21.3.2 Gene environment interplay 21.3.3 Summary 21.4 Cognitive aging in context 21.4.1 Lung function and cognitive aging 21.4.2 Socioeconomic status and cognitive aging 21.5 Future directions References Chapter 22 - Twin studies of smoking and tobacco use 22.1 Introduction 22.2 Natural history of smoking behavior 22.3 Twin studies past and present—the aim of the review 22.4 Genetic and environmental influences on smoking behavior 22.5 Beyond twins 22.6 Causes and consequences of tobacco use 22.7 Conclusion References Section 6 - Health Chapter 23 - Anthropometric twin studies 23.1 Introduction 23.2 Genetic and environmental variation in anthropometric measures 23.3 Birth outcomes 23.4 Height 23.5 Body mass index 23.6 Other anthropometric measures 23.7 Genetics of growth and development 23.8 Growth in height 23.9 Development of body mass index 23.10 Gene–environment interactions 23.11 Height 23.12 Body mass index 23.13 Conclusions References Chapter 24 - Twin studies of cardiorespiratory disease, daily cardiovascular activity and imaging 24.1 Introduction 24.2 Cardiorespiratory twin studies 24.2.1 Heritability of the most common cardiovascular diseases 24.2.1.1 Hypertension: blood pressure, blood pressure components, and vascular elasticity 24.2.1.2 Carotid atherosclerosis 24.2.1.3 Coronary atherosclerosis 24.2.1.4 Aortic atherosclerosis and aneurysm 24.2.1.5 Peripheral arterial disease 24.2.2 Twin studies in frequent respiratory diseases 24.2.2.1 Lung function 24.3 Twin studies of common chronic lung diseases 24.3.1 Chronic obstructive pulmonary disease (COPD) 24.3.2 Chronic bronchitis 24.3.3 Asthma 24.3.4 Lung cancer 24.3.5 Exhaled biomarkers 24.3.6 Obstructive sleep apnoea (OSA) 24.3.7 In conclusion 24.4 Gaining insight into the heritability of everyday cardiovascular function by twin studies 24.4.1 Introduction 24.4.2 Ambulatory studies of blood pressure and heart rate 24.4.3 Ambulatory monitoring of other cardiovascular parameters 24.4.4 In conclusion 25.5 Imaging of twins 25.5.1 X-ray 25.5.2 Breast mammography 25.5.3 Ultrasound 25.5.4 Computed tomography (CT) 25.5.5 Magnetic resonance imaging (MRI) 25.5.6 Neuroimaging 25.6 Future directions: radiogenomics and imaging epigenetics References Chapter 25 - Pediatric twin studies 25.1 Introduction 25.2 Respiratory and allergic diseases 25.2.1 Causes 25.2.2 Consequences 25.3 Autoimmune disorders 25.4 Hemato-oncological disorders 25.5 Comorbidity 25.6 Conclusion References Chapter 26 - Twin-singleton differences 26.1 Why are twin-singleton differences of interest to twin research generally? 26.2 Intrauterine and perinatal twin-singleton differences 26.2.1 Intrauterine growth 26.2.2 Intrauterine risk factors occurring in twins but not in singletons 26.2.2.1 Discordant fetal growth 26.2.2.2 Twin-to-twin transfusion 26.2.2.3 Twin testosterone transfer 26.2.2.4 Spontaneous single intrauterine fetal death 26.2.3 Congenital malformations 26.2.4 Perinatal mortality 26.3 Twin-singleton differences in development 26.3.1 Neurodevelopment 26.3.1.1 Cerebral palsy 26.3.1.2 Cognition 26.3.1.3 School grades, academic achievements, and vocational career 26.3.1.4 Neurodevelopment in single twins 26.3.1.5 The impact of assisted reproductive technology and socioeconomic position 26.3.2 Anthropometric development 26.3.2.1 Height and body mass index 26.4 Twin-singleton differences in behavior and personality 26.4.1 Lifestyle factors 26.4.2 Behavior 26.4.3 Personality 26.4.4 Divorce 26.5 Twin-singleton differences in morbidity and survival 26.5.1 Early life morbidity and survival 26.5.2 Adulthood morbidity and survival 26.5.2.1 The fetal origins hypothesis 26.5.2.2 Morbidity 26.5.2.3 Survival 26.6 Twin-singleton differences in genetic studies 26.7 Conclusion References Chapter 27 - Twin studies of puberty and behavior 27.1 What is puberty? 27.2 Measuring puberty 27.3 Variations in puberty: Gene and environment 27.4 Twin studies of puberty 27.4.1 Heritability of pubertal timing 27.4.2 Twin studies of links between puberty and behavior 27.5 Other uses of twin data on puberty when studying behavior 27.5.1 Replication analyses 27.5.2 Examining sex differences 27.6 Methodological issues 27.7 Future directions 27.7.1 Studying links between puberty and the brain 27.7.2 Potential impact of cultural differences 27.7.3 Continued use of the discordant design 27.7.4 Addressing limitations 27.8 Conclusion 27.9 Takeaways References Chapter 28 - Musculoskeletal twin studies 28.1 Introduction (MSK conditions) 28.2 How twins can help musculoskeletal research 28.2.1 The classical twin design in musculoskeletal research 28.2.2 The cotwin control design in musculoskeletal research 28.2.2.1 The cotwin control design in noninterventional musculoskeletal studies 28.2.2.2 Working with twins in randomized controlled trials References Chapter 29 - Contributions of twin studies to cancer epidemiology 29.1 Introduction 29.2 Risk of cancer in twins compared to singletons 29.3 Patterns of occurrence of cancer in twins 29.4 Studies of acquired risk factors for cancer in twins 29.5 Intraplacental metastasis of infantile leukemia 29.6 Cancer treatment, screening and survivorship in twins 29.7 A novel epidemiological approach to quantify the familial and non-familial, genetic and non-genetic, measured and ... 29.7.1 Variance of Age-specific Log Incidence Decomposition (VALID) 29.7.2 Measuring risk discrimination 29.7.3 The familial risk ratio caused by the familial aspects of a risk factor 29.7.4 Modeling the familial causes of variance in risk 29.7.5 Application of variance of age-specific incidence decomposition (VALID) 29.7.5.1 (i) Unmeasured familial factors 29.7.5.2 (ii) Measured familial factors 29.8 Summary References Chapter 30 - Epigenetic studies of neurodevelopment in twins 30.1 Introduction 30.2 The role of epigenetics in neurodevelopmental disorders 30.2.1 The developmental origins of health and disease (DOHaD) hypothesis 30.2.2 Epigenetic mechanisms 30.3 The role of twins in studying epigenetics of NDDs 30.3.1 Twin models 30.3.2 The use of twin models in epigenetic studies 30.4 Epigenetic twin studies in autism spectrum disorder 30.5 Epigenetic twin studies in attention-deficit hyperactivity disorder 30.6 Epigenetic twin studies of dimensions of cognitive development 30.7 Epigenetic twin studies in cerebral palsy 30.8 Epigenetic twin studies in epilepsy 30.9 Current issues for study of NDDs in twins 30.9.1 Can twin studies tease out cause versus effect? 30.9.2 Incidence of neurodevelopmental disorders in twins versus singletons 30.9.3 Choice and availability of tissue samples 30.9.4 Study sample sizes and power of epigenetic analyses 30.10 The future of twin studies in contributing to understanding the role of epigenetics in neurodevelopmental disorders References Chapter 31 - Contributions of twin research to the study of Alzheimer’s disease and related dementias 31.1 Genetic and environmental influences of ADRD 31.1.1 Sex differences 31.1.2 Age at onset 31.1.3 Intermediate ADRD phenotypes 31.2 Evaluating ADRD risk and protective factors 31.2.1 Co-twin control studies 31.2.2 Opposite sex twins 31.3 A new conceptualization of Alzheimer’s disease and related dementias 31.4 Summary and future directions References Section 7 - Twin Research: Genetics, Epigenetics, Microbiome, and Environmental Adaptation Chapter 32 - Twins and omics: the role of twin studies in multi-omics 32.1 Introduction 32.2 Genomics 32.2.1 What is genomics and how do we measure the genome? 32.2.2 Sequence differences between monozygotic twins 32.2.3 Sequence differences between dizygotic twins 32.3 Epigenomics 32.3.1 What is epigenomics and how do we measure the epigenome? 32.3.2 Causes of epigenetic variation 32.3.3 MZ discordant design applied to epigenomics studies 32.4 Transcriptomics 32.4.1 What is transcriptomics and how do we measure the transcriptome? 32.4.2 Causes of variation in gene expression levels 32.4.3 MZ discordant design applied to transcriptomics studies 32.4.4 Other applications of twin research in transcriptomics studies 32.5 Metabolomics 32.5.1 What is metabolomics and how do we measure the metabolome? 32.5.2 Causes of variation in metabolite levels 32.5.3 MZ discordant design applied to metabolomics studies 32.5.4 Other application of twin research in metabolomics studies 32.6 Twin studies in other omics domains 32.7 Discussion 32.8 Conclusion Acknowledgments References Chapter 33 - Epigenetics 33.1 Introduction to epigenetics and epigenomics 33.1.1 DNA methylation 33.1.1.1 DNA methylation in diseases and traits 33.1.1.2 Genetic effects on DNA methylation 33.1.2 Histone modifications 33.1.3 Noncoding RNAs 33.1.4 Complex interactions between epigenetic marks 33.2 Challenges in epigenetic research 33.3 Value of twins in epigenetic research 33.3.1 Classical twin model 33.3.2 Within-pair comparisons 33.3.3 Inferring causality 33.4 Key findings from epigenetic studies involving twins 33.4.1 The contribution of the genome and environment to the establishment and maintenance of DNA methylation 33.4.1.1 Super similarity of MZ twins 33.4.1.2 MZ twinning 33.4.2 The contribution of epigenetic variation to phenotypic variation 33.4.3 Stability and drift of methylation in time 33.4.4 Inferring causality for epigenetic associations by using twins 33.4.5 Epigenetic aging 33.5 Technical and statistical methods in epigenetics 33.5.1 Methods to measure DNA methylation 33.5.2 Methods to analyze DNA methylation data 33.5.3 DNA methylation as a surrogate measure 33.6 Future of epigenetic twin studies References Chapter 34 - An experiment in cotwin control: Adaptation to space travel1 34.1 Introduction 34.2 Twins reared apart and together 34.3 Space travel: effects on adaptive systems 34.4 Review of findings: a twin in space 34.5 Discussion Acknowledgments References Chapter 35 - Environmental risk factors for neurodevelopmental disorders: Evidence from twin studies 35.1 Rationale and aims 35.2 Introduction 35.3 Zygosity and chorionicity 35.4 Twins as a model for developmental variation 35.5 The intrauterine environment 35.6 Twin to twin transfusion syndrome (TTTS) 35.7 Selective fetal growth restriction (sFGR) 35.8 Twin anemia–polycythemia sequence (TAPS) 35.9 Neurodevelopmental disorders 35.10 Attention-deficit hyperactivity disorder 35.11 Autism spectrum disorder 35.12 Cerebral palsy 35.13 Schizophrenia 35.14 Epilepsy 35.15 Environmental influences on neurodevelopment in twins 35.16 Maternal immune activation 35.17 Maternal obesity and gestational diabetes 35.18 Maternal hypertension 35.19 Maternal smoking 35.20 Alcohol 35.21 The female reproductive microbiome 35.22 Conclusion References Chapter 36 - Microbiome studies and twin research 36.1 Basic concepts of the microbiome and microbial analysis: what are the differences between classical microbiology and ... 36.2 Analytic approaches in microbiome studies 36.3 Assessing taxonomic composition, function, and diversity of microbial community 36.4 Microbiome associations with human diseases and the application of the knowledge to the treatment 36.5 Twin research for microbiome studies 36.6 Summary and conclusion References Chapter 37 - Chromosomal anomalies, monogenetic diseases, and leukaemia in twins 37.1 Genetic background 37.2 Mechanisms of twin discordance 37.3 Postzygotic chromosomal nondisjunction and chromosomal mosaicism 37.4 Different levels of triplet repeat expansion 37.5 Postzygotic point mutations 37.6 Skewed X-inactivation 37.7 Other epigenetic mechanisms 37.8 Copy number variations (CNVs) 37.9 The value of twin studies in leukaemia research Gene abbreviation list References Section 8 - Conclusion Summary and concluding ­statement Appendix—Resources Index Back cover