Beyond Our Genes: Pathophysiology of Gene and Environment Interaction and Epigenetic Inheritance

Preface
Contents
Part I: The Physiology of Gene/Environment Interaction
	Chapter 1: Food and Nutrition as Prime Environmental Factors
		1.1 Diet Quality
		1.2 Obesity and Overweight
		1.3 Deficiency and Malnutrition
		1.4 Interplay With Physical Activity
		1.5 Nutrition Across the Life Course
		1.6 Nutrition During Pregnancy
		1.7 Nutrition From Childhood to Early Adulthood
		1.8 Nutrition in Elderly
		1.9 Nutrition and Diet as Primary Environmental Factor for Disease Development
		References
	Chapter 2: Circadian Rhythms in Health and Disease
		2.1 The Mammalian Circadian System
			2.1.1 The Circadian Clock
			2.1.2 The Mammalian Molecular Clock Machinery
			2.1.3 The Circadian Clock Regulates Overall Physiology
		2.2 The Circadian Clock in Relation to the Environment
			2.2.1 The Circadian System Is in Synchrony with the Environment
			2.2.2 Environmental Factors Can Disturb the Circadian Organization
		2.3 The Circadian Clock and Diseases
			2.3.1 Circadian Regulation of Metabolic Functions
			2.3.2 Circadian Control of the Immune Response
			2.3.3 The Circadian Clock and Environmental Factors Control Microbiome Fluctuations
			2.3.4 Environmental Changes Promote Cancer Through Clock Dysfunction
		2.4 Chapter Conclusion
		References
	Chapter 3: Environmental Factors’ Interference in Endocrine Aspects of Male Reproduction
		3.1 Environmental Factors as Endocrine Disruptors: Sources and Milestones of Endocrine Disruptors’ History
		3.2 EDCs as Obesogens
		3.3 Endocrine System as Physiological Interface With the Environment: Obesogens Perturbations of Hypothalamic-Pituitary-Gonadal (HPG) Axis
		3.4 Effects of Obesogens: Mechanisms of Regulation of Male Reproductive System Physiology
			3.4.1 Obesogens and Hormonal Disorders
			3.4.2 Obesogens and Testosterone
			3.4.3 Obesogens and Leptin
			3.4.4 Obesogens and Insulin
			3.4.5 Obesogens and Histopathology of the Testis and Sperm Parameters
		References
	Chapter 4: Prenatal Exposure to Endocrine Disrupting Chemicals and Their Effect on Health Later in Life
		4.1 Endocrine Disrupting Chemicals and Their Effects on the Endocrine System
			4.1.1 Rapid Increase of Chemical Exposure During the Last Decades
			4.1.2 What is an EDC?
			4.1.3 We Are Exposed to EDCs Throughout Our Life
			4.1.4 Fetuses are More Vulnerable to EDCs Than Adults
			4.1.5 Endocrine Systems Affected by EDCs
		4.2 The Effect of EDCs on Epigenetics as a Possible Explanation for Their Life Long Effects
			4.2.1 EDC Exposure During Fetal Development Alters DNA Methylation
			4.2.2 Transgenerational Effects
		4.3 Rapid Increase of Chronic Common Diseases – A Possible Connection to Prenatal EDC Exposure?
		4.4 Fertility Problems
			4.4.1 Introduction
			4.4.2 Associations Between Prenatal EDC Exposure and Fertility Problems in Adulthood
			4.4.3 Endocrine Disrupting Properties & EDC-Induced DNA Methylation Associated With Reproductive Capacity
		4.5 Neurodevelopmental Disorders
			4.5.1 Introduction
			4.5.2 Associations Between Prenatal EDC Exposure and Neurodevelopmental Health Outcomes
			4.5.3 Endocrine Disrupting Properties & EDC-Induced DNA Methylation Associated With Neurodevelopment
		4.6 Metabolic Disorders
			4.6.1 Introduction: Obesity and Diabetes
			4.6.2 Associations Between Prenatal EDC Exposure and the Metabolic Disorders Obesity and Diabetes
			4.6.3 Endocrine Disrupting Properties & EDC-Induced DNA Methylation Associated With Metabolic Disorders
		4.7 Conclusion
		References
Part II: Gene-Environment Interaction and Disease Susceptibility
	Chapter 5: Gene-Environment Interaction and Individual Susceptibility to Metabolic Disorders
		5.1 Introduction
		5.2 Genetic Susceptibility to Obesity and T2D
		5.3 The Relationship Between Genetic and Environmental Factors in Obesity and T2D
		5.4 Genetics of Obesity
		5.5 Genetics of Body Fat Distribution
		5.6 Genetics of Type 2 Diabetes
		5.7 Gene Environment Interaction
		5.8 Gene Environment Interaction in Obesity
			5.8.1 Obesogenic Environment
			5.8.2 Diet
			5.8.3 Physical Activity
			5.8.4 Effects of Combined Life-Style Modifications in Relation to Genetic Risk
			5.8.5 Smoking
			5.8.6 Sleep
		5.9 Gene Environment Interaction and T2D
			5.9.1 Diet
			5.9.2 Physical Activity
		5.10 Limitations
		5.11 Conclusions
		References
	Chapter 6: Gene-Environment Interaction and Cancer
		6.1 Cancer as Epigenetic Disease
		6.2 Environmental Hits on Cancer Progression
			6.2.1 Nutrition and Metabolism
			6.2.2 Endocrine Disruptors
			6.2.3 Circadian Rhythm
		6.3 Conclusions
		References
	Chapter 7: The Role of Gene-Environment Interaction in Mental Health and Susceptibility to the Development of Psychiatric Disorders
		7.1 Introduction: Gene-Environment Interactions (GxE) and Psychiatric Disorders
		7.2 Review of Gene-Environment Interaction Research in Psychiatric Disorders
			7.2.1 Candidate GxE Research
			7.2.2 Genome-Wide GxE Research
		7.3 Critical Evaluation of GxE Research in Psychiatric Disorders
			7.3.1 Theoretical Models of Gene-Environment Interaction
			7.3.2 Methodological Limitations of Candidate and Genome-Wide GxE Studies
			7.3.3 Gene-Environment Correlations
			7.3.4 GxE From a Life Course Perspective
			7.3.5 Specificity of GxE Effects in Predicting Psychiatric Disorders
		7.4 Future Directions
			7.4.1 Intermediate Phenotypes
			7.4.2 Experimental Studies
			7.4.3 Alternative Theoretical Models of Gene-Environment Interaction
		7.5 Conclusion
		References
	Chapter 8: Gene/Environment Interaction and Autoimmune Disease
		8.1 Introduction
			8.1.1 What Are Autoimmune Diseases
			8.1.2 Genetic Factors Associated with Autoimmune Diseases
			8.1.3 Environmental Factors Associated with Autoimmune Diseases
			8.1.4 The Microbiome
		8.2 Gene/Environment Interaction and Autoimmune Disease
			8.2.1 Inflammatory Bowel Diseases
			8.2.2 Gene-Cigarette Smoke Interaction in IBD
			8.2.3 Gene-Microbe Interaction in IBD
			8.2.4 Psoriasis
			8.2.5 Genetics
			8.2.6 Environment
				8.2.6.1 Ultra-violet light
				8.2.6.2 Smoking
				8.2.6.3 Infection and the Microbiome
			8.2.7 Rheumatoid Arthritis
			8.2.8 Environment
				8.2.8.1 Smoking
				8.2.8.2 Infection and the Microbiome
		References
Part III: Genome/Epigenome
	Chapter 9: Introduction to Epigenetic Inheritance: Definition, Mechanisms, Implications and Relevance
		9.1 Introduction to the Concept of Epigenetic Inheritance
		9.2 Developmental Windows of Susceptibility
		9.3 Overview of the Mechanisms of Epigenetic Inheritance in Mammals
			9.3.1 DNA Methylation and Genomic Imprinting
			9.3.2 Histone Post-Translational Modifications
			9.3.3 Small Non-coding RNAs
		9.4 The Relevance of Epigenetic Inheritance to Phenotypic Adaptation and Disease Risk
		9.5 Conclusion
		References
	Chapter 10: The (not so) Controversial Role of DNA Methylation in Epigenetic Inheritance Across Generations
		10.1 Methylation of Cytosine Represses Gene Expression in Mammals
		10.2 Epigenetic Inheritance – It All Began in Plants …
		10.3 Detection of DNA Methylation: Current and Coming Technologies
		10.4 Reprogramming the Early Mammalian Embryo
			10.4.1 Hit Me Once: Reprogramming the Pre-implantation Embryo
			10.4.2 Hit Me Twice: Reprogramming from Primordial Germ Cells to Gonocytes
		10.5 Inter- and Transgenerational Epigenetic Inheritance in Mammals
			10.5.1 Metabolic Health and Epigenetic Inheritance
			10.5.2 Anxiety and Epigenetic Inheritance
			10.5.3 Cognitive Plasticity and Epigenetic Inheritance
			10.5.4 Hepatic Wound Healing and Epigenetic Inheritance
			10.5.5 Parental Imprinting: Making Male and Female Gametes Compatible for Embryogenesis
			10.5.6 The Showcase Examples for DNA Methylation Associated Epigenetic Inheritance: The Agouti and Axin Epialleles
			10.5.7 Epimutations That Are Not Primary Epimutations: Methylation as Secondary Mode of Action
		10.6 Conclusion
		References
	Chapter 11: Small Non-Coding RNAs and Epigenetic Inheritance
		11.1 Introduction
		11.2 Gametogenesis
		11.3 Spermatozoal RNAs
			11.3.1 Long RNAs
			11.3.2 Small Non-Coding RNAs
		11.4 Origin of Sperm RNAs
			11.4.1 Testis-Derived RNAs
			11.4.2 Epididymal Contribution to Sperm RNA Profile
		11.5 Epigenetic Inheritance of Acquired Traits and Disorders Via Sperm RNAs
			11.5.1 Metabolic Disorders
			11.5.2 Traumatic Stress and Psychiatric Disorders
		11.6 How Inherited RNAs Can Affect the Development and Health of Offspring?
		11.7 Future Perspectives
		References
	Chapter 12: Future Perspectives in Epigenetic Inheritance
		12.1 Introduction
		12.2 Current Mechanistic Insights on Epigenetic Inheritance
			12.2.1 Paramutation and Epialleles
			12.2.2 DNA Methylation
			12.2.3 Small RNA
			12.2.4 Chromatin Structure
		12.3 Prospective Mechanisms
			12.3.1 Microbiome
			12.3.2 RNA Mediated Soma to Germ-Line Information Transfer
			12.3.3 Non-canonical Base Modifications
			12.3.4 Prions and Structural Inheritance
			12.3.5 Cellular Signaling and Feedback Loops
		12.4 Implications on Health and Well-being
			12.4.1 Environmental Health and Protection
			12.4.2 Pharmacovigilance
			12.4.3 ART and Preconception Care
		12.5 Outstanding Questions
		Glossary
		References
Index