Twin Research for Everyone: From Biology to Health, Epigenetics, and Psychology

Front cover
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Full title
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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
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