The power of two: epigenetics and twins

THG epigenetics blog post

This blog post was written by Jeff Craig

Special Epigenetics issue of Twin Research and Human Genetics

Twins are at the forefront of research into human health and disease. Twin Research and Human Genetics has published a Special Section highlighting how researchers have learned how epigenetics, the molecules that play the symphony of life on our genes, can influence our future health. Never before have such a group of papers been brought together in a single issue.

Papers highlight the power of sampling the same twins over time as their health changes and others detail the ways in which researchers scour the human genome for evidence of epigenetic associations with disease.

Four of the papers focus on the discordant identical twins in which only one twin has an illness. Topics span a wide age range of subjects, from birth weight to hormone replacement therapy (HRT). One even focuses on whether twins are “morning” or “evening” people.

Three papers from the Netherlands Twin Registry highlight the power of collecting biological samples from many hundreds, even thousands, of twin pairs. These are studies of aggressive behaviour, tic disorders and wellbeing and pinpoint specific epigenetic differences linked with each.

The final paper looks at the influences, both genetic and environmental, on how we age epigenetically.

In summary this special section is a clear snapshot of cutting edge twin research that is relevant for our hunt for the genes that influence all of our health.

You can read the articles included in this Special Section free of charge for a limited time here, or using the individual articles linked below.

See below for more details about the papers included in this special issue:

Read the full editorial from Jeff Craig and Richard Saffery, The Power of Two: Epigenetics and Twins

Chiarella et al: “This paper reviews the literature showing how monozygotic twin designs can be used to study epigenetic mechanisms that may explain the impact of early in utero and postnatal environmental factors on the development of psychopathology. “

Tsai et al: “this study of adult identical twins born with different weights found a biological legacy in a gene involved in fetal growth. This suggests that the environment we encounter in the womb can influence us for many year after.”

Bahl et al: “using twins discordant for hormone replacement therapy (HRT) the authors showed that HRT can change the activity of genes in the blood and that many of these genes were associated with sense of smell. This makes sense as HRT is known to improve a woman’s sense of smell.”

Wong et al: “believe it or not, some identical twins are more “day people” while their twin brither or sister are “night people. This study showed that our preference for day or night could be programmed in ‘epigenetic’ factors that stick to our genes and change their activity”

Du et al found an ingenious way to tell which of a pair of identical twins a sample found at a crime scene came from. Identical Twins cannot be distinguished because of their identical DNA but these researchers used “epigenetics”, factors that sit on top of the DNA”.

Bui et al: “identical teenage twins that had separate placentas in the womb may have a greater difference in the activity of their genes than those who shared a placenta. This shows that the environment we encounter in the womb can have long lasting effects”

Zilhao et al and van Dongen et al: “These twin studies of both tic disorders and aggressive behaviour identified changes to gene activity in the blood in genes related to brain function, suggesting that looking at the blood may reveal information about how such disorders are caused.”

Baselmans et al: “study showed that wellbeing in twins is associated with factors that control gene activity.“

Li et al: “study suggests that the variation in methylation acceleration due to unmeasured genetic factors is likely to be even lower that the 40% estimated in previous studies”

Announcing the publication of the first papers in GHEG

GHG blog image - cover
We are delighted to announce the publication of the first papers in Global Health, Epidemiology and Genomics. As GHEG is fully Open Access, these papers, and all papers published in the future, are freely accessible online. Here we provide a brief summary of our first three publications.

 A forum for global population health, technological advances and implementation science
 Manjinder Sandhu

A welcome editorial by our Editor in Chief, marking the launch of Global Health, Epidemiology and Genomics. Dr Sandhu highlights the strengths of the broad interdisciplinary scope of the journal and its international editorial board and invites the global health community to engage and contribute to the journal so that it becomes a valuable, practical and informative resource.
Read the full article here

 

favicon Study Profile: The Durban Diabetes Study (DDS): a platform for chronic disease research
 Thomas Hird et al.

A study profile of The Durban Diabetes Study (DDS), an on-going population-based cross-sectional survey of an urban black population in Durban, South Africa. The DDS was established to investigate a broad range of lifestyle, medical and genetic factors and their association with diabetes. It provides a rich platform for investigating the distribution, interrelation and aetiology of other chronic diseases and their risk factors, which can be utilised for other research studies.
Read the full article here

 

Favicon long Capitalizing on Natural Experiments in Low- to Middle- Income Countries to Explore Epigenetic Contributions to Disease Risk in Migrant Populations
 J. Jaime Miranda et al.

 

A commentary on the value of epigenetics as a tool for understanding differential disease risk in migrant populations. The authors highlight the merit of exploring migrant chronic disease risk in low- to middle-income countries, particularly in the context of rural-to-urban migration, with increasing urbanisation in this setting.
Read the full article here
More articles will be published in the coming weeks, and you can be notified when new articles are published by signing up to content alerts here. Here’s a preview of what’s coming soon:

  • H3Africa Multi-Centre Study of the Prevalence and Environmental and Genetic Determinants of Type 2 Diabetes in Sub-Saharan Africa: Study Protocol
    Kenneth Ekoru et al.
  • Regulatory Developments in the Conduct of Clinical Trials in India
    Dhvani Mehta and Ranjit Roy Chaudhury

GHEG accepts original research articles, brief reports, structured reviews and commentaries as well as protocols, research resources and analysis. We are waiving the Article Processing Charge for all articles submitted to GHEG before the end of 2016. We invite contributions from a range of disciplines:
Epidemiology, Clinical trials, Genetics, Observational studies, Qualitative studies, Anthropological studies, Social science, Community intervention, Health systems, Health services, Population genetics, Population history.
For further information on the journal and how to submit please visit our website. Or if you wish to submit your manuscript directly please visit: http://mc.manuscriptcentral.com/gheg.

Cambridge launch new open access journal – Global Health, Epidemiology and Genomics

GHG blog image - cover

Cambridge unveils new Open Access journal – Global Health, Epidemiology and Genomics (GHEG)

Cambridge University Press is delighted to announce a major new open access journal, Global Health, Epidemiology and Genomics (GHEG), dedicated to publishing and disseminating research that addresses and increases understanding of global and population health issues through the application of population science, genomics and applied technologies.

Global Health, Epidemiology and Genomics is the Press’s second Open Access journal in the field of global health, joining Global Mental Health which launched in 2014. Spanning both non-communicable and communicable diseases, GHEG will specifically integrate epidemiology, genomics and related technological advances in the global health context. Topics relevant to GHEG will include studies, methods and resources relating to global population health, disease aetiology, variation in disease susceptibility, drug resistance and surveillance, health care and health care systems, pharmacogenomics and stratified medicine, as well as the challenges of implementing new developments into clinical practice and the community, globally. In addition to more traditional Original Research and Review Articles, GHEG will support submission of Resources and Analyses that provide a framework for integrating and facilitating genomics and global health studies.

The Editor-in-Chief of GHEG is Dr Manjinder Sandhu, head of the Global Health Group based at the University of Cambridge and the Wellcome Trust Sanger Institute. The international Editorial team includes recognised leaders in global health, epidemiology and genomics from around the world who have taken a lead in shifting attention and action to global health and populations, as well as a wider Editorial Board that will reflect and emphasize the broad scope of the field.

Dr Sandhu said, “I am committed to making GHEG an innovative, engaging and practical resource for the global health research community through which we can publish new scientific research, exchange ideas within and across our related disciplines and share resources to facilitate efforts to increase our understanding of human health and shape effective disease management worldwide.”

Professor Alex Brown, Deputy Director of the South Australia Health & Medical Research Institute (SAHMRI) and one of the journal’s Associate Editors commented, “I am delighted to be involved with GHEG, an exciting venture which recognises the relevance and importance of the work being undertaken in the field of global health, epidemiology and genomics and the widespread benefits to be gained by applying technological advances and innovations to research into population health including within disadvantaged population groups. By facilitating discussion and encouraging the sharing of resources GHEG looks to actively support contributions in these areas.”

Katy Christomanou, Publishing Director for STM Journals at Cambridge University Press, added, “This launch affirms our long-term commitment in the global health field and reflects our strong investment in maintaining and extending our successful presence in this area. We are highly enthusiastic at the prospect of working alongside such an outstanding editorial team.”

Global Health, Epidemiology and Genomics will be hosted on Cambridge’s industry-leading platform, Cambridge Journals Online (CJO). The Journal will benefit from a range of the latest author services including article level usage metrics and Altmetric data. In addition, for articles submitted during 2015 and 2016, Cambridge University Press will waive all article processing charges.

For more information please visit the journal website: journals.cambridge.org/gheg

 

Cambridge launch new open access journal – Global Health, Epidemiology and Genomics

GHEG cover_final2

Cambridge unveils new Open Access journal – Global Health, Epidemiology and Genomics (GHEG)

Cambridge University Press is delighted to announce a major new open access journal, Global Health, Epidemiology and Genomics (GHEG), dedicated to publishing and disseminating research that addresses and increases understanding of global and population health issues through the application of population science, genomics and applied technologies.

Global Health, Epidemiology and Genomics is the Press’s second Open Access journal in the field of global health, joining Global Mental Health which launched in 2014. Spanning both non-communicable and communicable diseases, GHEG will specifically integrate epidemiology, genomics and related technological advances in the global health context. Topics relevant to GHEG will include studies, methods and resources relating to global population health, disease aetiology, variation in disease susceptibility, drug resistance and surveillance, health care and health care systems, pharmacogenomics and stratified medicine, as well as the challenges of implementing new developments into clinical practice and the community, globally. In addition to more traditional Original Research and Review Articles, GHEG will support submission of Resources and Analyses that provide a framework for integrating and facilitating genomics and global health studies.

The Editor-in-Chief of GHEG is Dr Manjinder Sandhu, head of the Global Health Group based at the University of Cambridge and the Wellcome Trust Sanger Institute. The international Editorial team includes recognised leaders in global health, epidemiology and genomics from around the world who have taken a lead in shifting attention and action to global health and populations, as well as a wider Editorial Board that will reflect and emphasize the broad scope of the field.

Dr Sandhu said, “I am committed to making GHEG an innovative, engaging and practical resource for the global health research community through which we can publish new scientific research, exchange ideas within and across our related disciplines and share resources to facilitate efforts to increase our understanding of human health and shape effective disease management worldwide.”

Professor Alex Brown, Deputy Director of the South Australia Health & Medical Research Institute (SAHMRI) and one of the journal’s Associate Editors commented, “I am delighted to be involved with GHEG, an exciting venture which recognises the relevance and importance of the work being undertaken in the field of global health, epidemiology and genomics and the widespread benefits to be gained by applying technological advances and innovations to research into population health including within disadvantaged population groups. By facilitating discussion and encouraging the sharing of resources GHEG looks to actively support contributions in these areas.”

Katy Christomanou, Publishing Director for STM Journals at Cambridge University Press, added, “This launch affirms our long-term commitment in the global health field and reflects our strong investment in maintaining and extending our successful presence in this area. We are highly enthusiastic at the prospect of working alongside such an outstanding editorial team.”

Global Health, Epidemiology and Genomics will be hosted on Cambridge’s industry-leading platform, Cambridge Journals Online (CJO). The Journal will benefit from a range of the latest author services including article level usage metrics and Altmetric data. In addition, for articles submitted during 2015 and 2016, Cambridge University Press will waive all article processing charges.

For more information please visit the journal website: journals.cambridge.org/gheg

Male sexual orientation influenced by genes

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Results of a five-year study of 409 independent pairs of homosexual brothers in 384 families find that genetics play a key role in male sexual orientation. Alan Sanders, M.D., a psychiatrist who studies behavioral genetics at NorthShore University HealthSystem Research Institute, was the principal investigator of the molecular genetics study that scanned the entire human genome to search for evidence of genetic links to variation in sexual orientation in men.

“We found two strong links in chromosome 8 and chromosome Xq28, which supports that this is not a one-gene, one-trait scenario,” said Dr. Sanders. “These genetic variations contribute to the development of the important psychological trait of male sexual orientation.

The new evidence “is not proof but it’s a pretty good indication” that genes on the two chromosomes have some influence over sexual orientation.”

Participants in the study were gay men with at least one living gay brother (full brothers, half brothers or fraternal twins). They were asked to provide DNA samples through blood or saliva and to complete a questionnaire about their sexual and personal history and that of immediate family members. The study was funded by the US National Institutes of Health from the National Institute for Child Health and Human Development.

“Understanding the origins of sexual orientation enables us to learn a great deal about sexual motivation, sexual identity, gender identity and sex differences,” Dr. Sanders added.

The full paper, “Genome-wide scan demonstrates significant linkage for male sexual orientation”, which is published in Psychological Medicine can be read free of charge for a limited time here.

Explore the online archive of AGMG

AGMG cover-1
Cambridge University Press and Twin Research and Human Genetics (TRHG) are proud to announce the release of the online archive of AGMG, the predecessor journal to TRHG. AGMG was the official journal of the International Society for Twin Studies (ISTS) from 1952-1998 when TRHG took over this role. However, both journals have always had a wider interest in the field of human genetics.

Twins can provide unique and powerful opportunities to study genetic and environmental factors that make people differ in how they look, behave and how healthy they are. Monozygotic [identical] twins share all their genetic variation and dizygotic [non-identical] twin pairs, on average, share about 50% of their genetic variation. Both types of twin pairs often but not always share similar pre- and post-natal environments as well. Having twins participate in these studies helps to continue important research for common human conditions such as diseases, health, and behaviors, leading to advances in science, medicine and future potential therapies.

Much effort has gone into creating this digitised archive and making it available online to the research community because we believe that many of the classic papers published in AGMG reveal the academic foundations of the subject and still have relevance today. Below is a link to the 20 most cited papers from the AGMG archive to demonstrate the wide scope of interest. We encourage you to explore and enjoy this fascinating resource.

View the 20 most-cited papers from the AGMG archive here .

The papers cover a wide spectrum of topics and include the following articles:

  • Population-Based Twin Registries: Illustrative Applications in Genetic Epidemiology and Behavioral Genetics from the Finnish Twin Cohort Study (1990)
  • Resting Metabolic Rate in Monozygotic and Dizygotic Twins (1985)
  • Causes of Variation in Drinking Habits in a Large Twin Sample (1984)
  • The Vanishing Twin (1982)

 

Psychiatric Genetic Revolution – is calcium the key?

DNA Rendering. Photo: ynse. used under CretaiveCommons

DNA Rendering. Photo: ynse. used under CreativeCommons

Dr. Berrettini and I published Principles of Psychiatric Genetics in late 2012. Since then, there have been several interesting developments in Psychiatric Genetics worth calling your attention to. The first is a set of articles from the Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC). The PGC has revolutionized the field of psychiatric genetics in the last decade by bringing together investigators from around the world to pool their carefully collected clinical samples in order to provide the numbers for powerful analyses of common gene variants in major psychiatric disorders such as schizophrenia and bipolar disorder. Whereas the original genome-wide association studies in psychiatry included ~1000 cases and 1000 controls, we are now able to amass collections of 25,000 cases with schizophrenia and 37,000 controls because investigators have come together under the PGC umbrella. This has provided the power to detect more than 100 common single gene variants associated with schizophrenia.

The particular article I wanted to feature was one from the Cross-Disorder Group in that consortium (Cross-Disorder Group of the PGC, Lancet, 2013). Samples were combined from persons with schizophrenia, bipolar disorder, depression, attention-deficit hyperactivity disorder, and autism. There were four single gene variants that were identified from the group of disorders considered together. The fascinating aspect of this was that two of the four were genes controlling calcium channels in the brain. The investigators were also able to test an entire group of calcium-channel related genes (72 genes in all) and demonstrate that variations in this set of gene markers was associated with vulnerability to these conditions, especially to schizophrenia and bipolar disorder. This is a new finding in psychiatry, and it is potentially very relevant to clinical management of these conditions. Calcium channel abnormalities have been described in these disorders, but this hypothesis was not central to a consideration of the neurobiology of these disorders. Over the past three decades, much more energy has been spent on theories involving neurotransmitters such as serotonin, dopamine, and norepinephrine. However, it may be that calcium channel signaling problems are causal to neurotransmitter variation. Calcium flow into the cell is necessary for cell excitation and signaling. Many of the critical second messenger systems in the cell (which carry a signal within the cell after a neurotransmitter hits its target receptor) are dependent on calcium.

Calcium channel inhibitors are available, and have been used to treat cardiovascular conditions for several decades (e.g., verapamil, nifedipine, nimodipine) . They have also been used to treat psychiatric conditions, with some success, but not consistent success. It may be that these agents must be targeted to specific individuals who demonstrate calcium channel gene abnormalities. Or it may be that newly designed drugs with more subtle effects on calcium activity are needed. In any case, this seems like an important clue with ramifications for our understanding of the biology of these disorders, as well as possible treatment strategies.

Another paper from the same group was published later in 2013 (Lee et al, Nature Genetics). This used a method for analyzing the heritability of medical conditions based on genome-wide data. Even if the power is not adequate to identify all of the gene variants individually, you can use the available information on gene arrays (small plastic chips that contain short sequences from every gene in the genome) to test whether or not you have captured some of the variation or not. It could be that testing every gene in the genome in this way would still not give you much information about diagnosis. This was thought to be the case for several years after these techniques were introduced. Many investigators felt that psychiatric disorders were simply too complex in their inheritance to be analyzed by the gene chips. There was too much “missing heritability” (evidence of inheritance from family studies that was not able to be tracked to variations at the gene level). This recent paper demonstrated convincingly that this idea is not true. The psychiatric disorders are analyzable at the level of individual gene variants and functions. We now can be confident that 25-40% of the reason that one person becomes ill with schizophrenia or major depression or autism while another person does not is related to common genetic variation that can be measured in the laboratory. We don’t yet know what all the pertinent genes do but we can anticipate that the answers will be available to us in the coming years. Part of the answer probably relates to calcium channel genes, as noted above.

There is another set of data from this paper that is tremendously important for our ideas of psychiatric diagnosis. For the past hundred years, we have clearly separated schizophrenia (a chronic disorder) and bipolar disorder (an episodic condition). There are different treatments for these conditions and different expectations for how well people will do in overcoming the symptoms. One of the lessons from the latest round of genetic analyses is that there is substantial overlap in the genetic vulnerability factors for the two disorders. The “covariance” between schizophrenia and bipolar disorder is 25-30%. Therefore we should expect that some of the disruption in neurobiological systems will be the same for the two disorders and some will be different. This is consistent with evidence from genetic linkage studies summarized by my colleague Dr. Berrettini some years ago and it is consistent with recent family studies as well. The new information, though, is more specific regarding the amount of overlap. It suggests that we should consider these two diseases similar in type and origin.

John I. Nurnberger, Jr. is co-editor of Principles of Psychiatric Genetics (out now).

Principles of Psychiatric Genetics

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