Why your genome isn’t your destiny

I’m all about individualized medicine. I highly recommend genetic testing, and genetic individuality is a foundational element of the NGmedicine approach. But genetic individuality is just ONE facet of the individuality of an organism. Epigenetics, biochemistry, and environmental factors can all significantly influence health and disease risk.

Growing up, I assumed that I was just unlucky to have eczema – it was written in my genes, and there was nothing I could do about it. The doctors said I might grow out of it, but by age 18, I was thoroughly unconvinced that I’d ever rid myself completely of the itchy, scaly rash.

It wasn’t until I started researching the links between diet, the gut microbiota, environmental exposures, and eczema that I really started to put the picture together, and I started making lifestyle changes that ultimately reversed my chronic skin condition.

Since then, I’ve had my genome sequenced, and I do in fact have several different gene variants that explain my eczema. But genes were just one small piece of the puzzle. Read on to learn why your genes aren’t your destiny, and how you can optimize your exposome to prevent and reverse chronic disease.

 

The history of genomics and biological determinism

In 1866, Mendel traced heredity in pea plants, showing that the inheritance of traits was governed by a set of simple rules. The discovery of the double-helix structure of DNA by Watson and Crick didn’t come until 1953. DNA was sequenced for the first time in 1977, and the Human Genome Project was completed in 2003.

Since 2003, genomics has taken off. The cost of sequencing has plummeted at a rate faster than predicted by Moore’s Law, and it will soon be possible to sequence a whole genome for a mere $1,000.1

Source: National Human Genome Research Institute

With clinical whole genome sequencing now a reality, there’s a lot of excitement for the idea that genetics will solve all human disease:

“Mapping the human genome has been compared with putting a man on the moon, but I believe it is more than that. This is the outstanding achievement not only of our lifetime, but in terms of human history.”

– Michael Dexter, director of the biomedical research charity The Welcome Trust

[The human genome is] “a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.”

– Francis Collins, Director of the Human Genome Project

 “We now have the possibility of achieving all we ever hoped for from medicine.”

– David John Sainsbury, Former UK Minster for Science and Innovation

This concept of “genetic determinism” led many to believe that mapping the human genome would identify definitive links between genes and disease. Enter the age of GWAS.

 

Genome-Wide Association Studies identify gene-disease links

You may have heard of “genome wide association studies”, or GWAS. These studies perform whole genome sequencing on a very large population to determine gene variants that are found more frequently in people with a particular diseases. The number of gene-disease associations is growing rapidly. Just some examples of GWAS published in the last few months include:

  • Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.2
  • Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14.3
  • Enhanced identification of potential pleiotropic genetic variants for bone mineral density and breast cancer.4

NIH even has a GWAS catalog to keep track of them all.

 

Genes alone can’t explain chronic disease

But even with new GWAS being published every month, the amount of chronic disease that can be explained by genetics is small. Take IBD, for example. Over 231 individual gene variants within 200 different genes are associated with IBD risk. Yet genetics still only explain 13.1% and 8.2% of the total variance in disease for Crohn’s disease and ulcerative colitis, respectively.5

“We simply don’t have enough genes for this idea of biological determinism to work.”

– Craig Venter, founder of The Institute for Genomic Research

Studies have also looked at disease concordance in identical (monozygotic) twins. In other words, if both twins have the same genome, and one twin has a disease, what is the chance that the other twin will have it as well? Look at the results for the following diseases, reviewed in a paper by Castillo-Fernandez et al. in 2014:6

  • Type 1 diabetes: 61% concordance
  • Type 2 diabetes: 41% concordance
  • Autism: 58-60% concordance
  • Schizophrenia: 58% concordance
  • Cancer: 0-16% concordance

Through statistical analysis of twin studies for 28 different chronic diseases, scientists have estimated that genes account for less than 16.4% of chronic disease.7

Castillo-Fernandez et al. write: “… for many complex traits, genotype alone may not fully determine phenotypic variation, and the interplay between genes and environment needs to be considered.6

 

A flashback to Darwinian times

In the early 1800s, several early naturalists sought to develop theories about how life on Earth came to be the way it was.

Jean-Baptiste Lamarck argued that changes in organisms could occur within a generation or two. He proposed that animals acquired particular traits during their lifetime as a result of their interaction with their environment. The most oft used example is that giraffes acquired their long necks because their recent ancestors had stretched to reach the leaves on taller trees.

In contrast, Charles Darwin argued that organisms changed over millions of years due to natural genetic variation in the population. Among giraffes in the population, those who happened to have the longest necks tended to be more likely to find food, survive, and reproduce.

     

Ultimately, Darwin’s theory won the day, and natural selection is how we look at inheritance today. Meanwhile, Lamarck’s theory of acquired characteristics came to be seen as a colossal scientific blunder.

But was it? Could Lamarck simply have anticipated what we now know to be epigenetics?

 

Epigenetics: the genetic “switch”

Epigenetics is the study of the biological mechanisms that switch genes “on” and “off”. These mechanisms act by changing the structure of DNA, not the DNA sequence.

In the nucleus of every cell in our body, DNA is wound around proteins called histones. When the histones are packed very tightly, the message encoded in the DNA cannot be transcribed. The gene won’t be made into a protein, and is effectively switched “off”. On the other hand, when the histones and their associated DNA pack more loosely, enzymes can bind and initiate transcription of the DNA message. This is the first step towards making a protein from the gene, so the gene is said to be “expressed” or “on”.

 

Certain enzymes can add or remove epigenetic “tags” that influence whether DNA is loosely or tightly packaged, and therefore whether its genes are expressed. Thanks to modern science, we have techniques that can measure the type and amount of tags on a particular gene.

“We believe that many diseases that have aberrant gene expression at their root can be linked to how DNA is packaged […] it’s now one of the most promising areas of health-related research.”

– Rod Dashwood, professor of Environmental and Molecular Toxicology

Indeed, epigenetic alterations have been reported in autoimmune diseases,8 diabetes,9 asthma,10 Alzheimer’s disease,11 and Parkinson’s disease,12 to name a few.

Moreover, epigenetic modifications are passed on to offspring. In this way, traits can be acquired in just one or two generations, suggesting that Lamarck’s hypothesis of acquired characteristics wasn’t so farfetched after all. While a giraffe stretching its neck isn’t likely to cause epigenetic changes, many other environmental factors will. Enter the exposome.

 

The exposome and your health

If genes account for less than 16% of chronic disease, the environment is responsible for the remaining 84%. In other words, it’s the interaction between our environment and our genes that determines whether we remain healthy or develop disease. Your genes might predispose you to certain diseases, but it’s the environmental factors that tip the scale one way or the other.

Originally proposed by cancer epidemiologist Dr. Christopher Wild in 2005, the “exposome” encompasses all environmental exposures from before conception to adulthood.13 It includes everything we eat, drink, breathe, put on our skin, our social interactions, what our parents ate before we were conceived, whether we were breastfed, and even our state of mind.

“Unlike the genome, the exposome is a highly variable and dynamic entity that evolves throughout the lifetime of the individual.”

At one time, scientists thought that our DNA held the key to preventing and reversing disease – that our genes were our destiny. We now know that this isn’t true – the environment, and not our genes, is the primary driver of health and longevity. And by taking control of our exposome, we have the power to prevent and reverse chronic disease.

“We have been led to believe that our genes determine the character of our lives, yet new research surprisingly reveals that it is the character of our lives that controls our genes. Rather than being victims of our heredity, we are actually masters of our genome.”

– Bruce Lipton, author of “The Biology of Belief”

Indeed, several studies have found that epigenetic changes are not permanent. One study found that supplementing the diet of mice with methyl donors like vitamin B12 reversed the negative epigenetic alterations caused by poor maternal care.14 Another study found that the natural bioactive compound berberine was able to reverse the epigenetic changes and ameliorate fatty liver disease caused by a poor diet.15

 

How to optimize your exposome and epigenome

We, too, can alter our epigenetics, and our future health as a result. In less than ten years, we’ll likely have affordable technology to measure and track changes in our epigenomes in real-time. Until then, here are several evidence-based ways to optimize your exposome and reduce your risk of chronic disease:

  • Eat a nutrient-dense diet that is appropriate for humans. Make sure that you consume plenty of folate, choline, and vitamin B12, which are important for regulating gene expression.
  • Get plenty of low-level physical activity interspersed with higher intensity exercise. Through epigenetic regulation, exercise has been shown to increase expression of brain-derived neurotrophic factor (BDNF), which stimulates neurogenesis and synapse formation.16
  • Avoid environmental toxins. Exposure to synthetic chemicals or heavy metals has epigenetic consequences. For instance, Bisphenol A, phthalates, arsenic, and mercury have all been shown to negatively impact gene expression.17–19
  • Get plenty of sleep. Just one night of sleep deprivation has been shown to cause altered expression of clock genes in key metabolic tissues.17
  • Manage stress and make time for play. One study found that environmental enrichment was able to reverse the negative epigenetic changes that resulted from prenatal stress.21
  • Support your microbiome. Having your microbiome sequenced can often be more valuable than having whole genome sequencing, as 99% of the genes in your body are microbial and the microbiota heavily influences host epigenetics. For example, when bacteria ferment fiber, they produce a metabolite called butyrate, an incredibly potent epigenetic activator of anti-inflammatory genes.22
  • Look for potential “clues” in your genome. While genes aren’t your destiny, genetic information can still be useful to provide “clues” as to what part of your exposome might be important. For example, my raw genome data revealed a PEMT mutation, which suggested that I might benefit from supplemental choline.23

How will you hack your exposome? Let me know in the comments and be sure to subscribe below!

If you want help interpreting your genetic results or optimizing your epigenome, you can also check out my health coaching services and get a free first consultation.

 

Sources:

  1. The Cost of Sequencing a Human Genome. National Human Genome Research Institute (NHGRI) Available at: https://www.genome.gov/27565109/The-Cost-of-Sequencing-a-Human-Genome. (Accessed: 1st November 2017)
  2. Hong, X. et al. Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth. Nat Commun 8, 15608 (2017).
  3. Takahashi, Y. et al. Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14. Cancer Sci. 108, 2239–2247 (2017).
  4. Peng, C. et al. Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer. Calcif Tissue Int 101, 489–500 (2017).
  5. Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47, 979–986 (2015).
  6. Castillo-Fernandez, J. E., Spector, T. D. & Bell, J. T. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med 6, (2014).
  7. Rappaport, S. M. Genetic Factors Are Not the Major Causes of Chronic Diseases. PLoS One 11, (2016).
  8. Ballestar, E. Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol 39, 30–41 (2010).
  9. Rakyan, V. K. et al. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 7, e1002300 (2011).
  10. Salam, M. T., Zhang, Y. & Begum, K. Epigenetics and childhood asthma: current evidence and future research directions. Epigenomics 4, 415–429 (2012).
  11. Sanchez-Mut, J. V. et al. DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain 136, 3018–3027 (2013).
  12. Masliah, E., Dumaop, W., Galasko, D. & Desplats, P. Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics 8, 1030–1038 (2013).
  13. Wild, C. P. Complementing the genome with an ‘exposome’: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev. 14, 1847–1850 (2005).
  14. Weaver, I. C. G. et al. Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life. J. Neurosci. 25, 11045–11054 (2005).
  15. Chang, X. et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res 51, 2504–2515 (2010).
  16. Gomez-Pinilla, F., Zhuang, Y., Feng, J., Ying, Z. & Fan, G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. European Journal of Neuroscience 33, 383–390 (2011).
  17. Singh, S. & Li, S. S.-L. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates. International Journal of Molecular Sciences 13, 10143–10153 (2012).
  18. Ren, X. et al. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ. Health Perspect. 119, 11–19 (2011).
  19. Onishchenko, N., Karpova, N., Sabri, F., Castrén, E. & Ceccatelli, S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J. Neurochem. 106, 1378–1387 (2008).
  20. Cedernaes, J. et al. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men. J Clin Endocrinol Metab 100, E1255–E1261 (2015).
  21. Morley-Fletcher, S., Rea, M., Maccari, S. & Laviola, G. Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats. European Journal of Neuroscience 18, 3367–3374 (2003).
  22. Berni Canani, R., Di Costanzo, M. & Leone, L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics 4, 4 (2012).
  23. da Costa, K.-A. et al. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 20, 1336–1344 (2006).

 

Why your genome isn’t your destiny

I’m all about individualized medicine. I highly recommend genetic testing, and genetic individuality is a foundational element of the NGmedicine approach. But genetic individuality is just ONE facet of the individuality of an organism. Epigenetics, biochemistry, and environmental factors can all significantly influence health and disease risk.

Growing up, I assumed that I was just unlucky to have eczema – it was written in my genes, and there was nothing I could do about it. The doctors said I might grow out of it, but by age 18, I was thoroughly unconvinced that I’d ever rid myself completely of the itchy, scaly rash.

It wasn’t until I started researching the links between diet, the gut microbiota, environmental exposures, and eczema that I really started to put the picture together, and I started making lifestyle changes that ultimately reversed my chronic skin condition.

Since then, I’ve had my genome sequenced, and I do in fact have several different gene variants that explain my eczema. But genes were just one small piece of the puzzle. Read on to learn why your genes aren’t your destiny, and how you can optimize your exposome to prevent and reverse chronic disease.

 

The history of genomics and biological determinism

In 1866, Mendel traced heredity in pea plants, showing that the inheritance of traits was governed by a set of simple rules. The discovery of the double-helix structure of DNA by Watson and Crick didn’t come until 1953. DNA was sequenced for the first time in 1977, and the Human Genome Project was completed in 2003.

Since 2003, genomics has taken off. The cost of sequencing has plummeted at a rate faster than predicted by Moore’s Law, and it will soon be possible to sequence a whole genome for a mere $1,000.1

Source: National Human Genome Research Institute

With clinical whole genome sequencing now a reality, there’s a lot of excitement for the idea that genetics will solve all human disease:

“Mapping the human genome has been compared with putting a man on the moon, but I believe it is more than that. This is the outstanding achievement not only of our lifetime, but in terms of human history.”

– Michael Dexter, director of the biomedical research charity The Welcome Trust

[The human genome is] “a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.”

– Francis Collins, Director of the Human Genome Project

 “We now have the possibility of achieving all we ever hoped for from medicine.”

– David John Sainsbury, Former UK Minster for Science and Innovation

This concept of “genetic determinism” led many to believe that mapping the human genome would identify definitive links between genes and disease. Enter the age of GWAS.

 

Genome-Wide Association Studies identify gene-disease links

You may have heard of “genome wide association studies”, or GWAS. These studies perform whole genome sequencing on a very large population to determine gene variants that are found more frequently in people with a particular diseases. The number of gene-disease associations is growing rapidly. Just some examples of GWAS published in the last few months include:

  • Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.2
  • Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14.3
  • Enhanced identification of potential pleiotropic genetic variants for bone mineral density and breast cancer.4

NIH even has a GWAS catalog to keep track of them all.

 

Genes alone can’t explain chronic disease

But even with new GWAS being published every month, the amount of chronic disease that can be explained by genetics is small. Take IBD, for example. Over 231 individual gene variants within 200 different genes are associated with IBD risk. Yet genetics still only explain 13.1% and 8.2% of the total variance in disease for Crohn’s disease and ulcerative colitis, respectively.5

“We simply don’t have enough genes for this idea of biological determinism to work.”

– Craig Venter, founder of The Institute for Genomic Research

Studies have also looked at disease concordance in identical (monozygotic) twins. In other words, if both twins have the same genome, and one twin has a disease, what is the chance that the other twin will have it as well? Look at the results for the following diseases, reviewed in a paper by Castillo-Fernandez et al. in 2014:6

  • Type 1 diabetes: 61% concordance
  • Type 2 diabetes: 41% concordance
  • Autism: 58-60% concordance
  • Schizophrenia: 58% concordance
  • Cancer: 0-16% concordance

Through statistical analysis of twin studies for 28 different chronic diseases, scientists have estimated that genes account for less than 16.4% of chronic disease.7

Castillo-Fernandez et al. write: “… for many complex traits, genotype alone may not fully determine phenotypic variation, and the interplay between genes and environment needs to be considered.6

 

A flashback to Darwinian times

In the early 1800s, several early naturalists sought to develop theories about how life on Earth came to be the way it was.

Jean-Baptiste Lamarck argued that changes in organisms could occur within a generation or two. He proposed that animals acquired particular traits during their lifetime as a result of their interaction with their environment. The most oft used example is that giraffes acquired their long necks because their recent ancestors had stretched to reach the leaves on taller trees.

In contrast, Charles Darwin argued that organisms changed over millions of years due to natural genetic variation in the population. Among giraffes in the population, those who happened to have the longest necks tended to be more likely to find food, survive, and reproduce.

     

Ultimately, Darwin’s theory won the day, and natural selection is how we look at inheritance today. Meanwhile, Lamarck’s theory of acquired characteristics came to be seen as a colossal scientific blunder.

But was it? Could Lamarck simply have anticipated what we now know to be epigenetics?

 

Epigenetics: the genetic “switch”

Epigenetics is the study of the biological mechanisms that switch genes “on” and “off”. These mechanisms act by changing the structure of DNA, not the DNA sequence.

In the nucleus of every cell in our body, DNA is wound around proteins called histones. When the histones are packed very tightly, the message encoded in the DNA cannot be transcribed. The gene won’t be made into a protein, and is effectively switched “off”. On the other hand, when the histones and their associated DNA pack more loosely, enzymes can bind and initiate transcription of the DNA message. This is the first step towards making a protein from the gene, so the gene is said to be “expressed” or “on”.

 

Certain enzymes can add or remove epigenetic “tags” that influence whether DNA is loosely or tightly packaged, and therefore whether its genes are expressed. Thanks to modern science, we have techniques that can measure the type and amount of tags on a particular gene.

“We believe that many diseases that have aberrant gene expression at their root can be linked to how DNA is packaged […] it’s now one of the most promising areas of health-related research.”

– Rod Dashwood, professor of Environmental and Molecular Toxicology

Indeed, epigenetic alterations have been reported in autoimmune diseases,8 diabetes,9 asthma,10 Alzheimer’s disease,11 and Parkinson’s disease,12 to name a few.

Moreover, epigenetic modifications are passed on to offspring. In this way, traits can be acquired in just one or two generations, suggesting that Lamarck’s hypothesis of acquired characteristics wasn’t so farfetched after all. While a giraffe stretching its neck isn’t likely to cause epigenetic changes, many other environmental factors will. Enter the exposome.

 

The exposome and your health

If genes account for less than 16% of chronic disease, the environment is responsible for the remaining 84%. In other words, it’s the interaction between our environment and our genes that determines whether we remain healthy or develop disease. Your genes might predispose you to certain diseases, but it’s the environmental factors that tip the scale one way or the other.

Originally proposed by cancer epidemiologist Dr. Christopher Wild in 2005, the “exposome” encompasses all environmental exposures from before conception to adulthood.13 It includes everything we eat, drink, breathe, put on our skin, our social interactions, what our parents ate before we were conceived, whether we were breastfed, and even our state of mind.

“Unlike the genome, the exposome is a highly variable and dynamic entity that evolves throughout the lifetime of the individual.”

At one time, scientists thought that our DNA held the key to preventing and reversing disease – that our genes were our destiny. We now know that this isn’t true – the environment, and not our genes, is the primary driver of health and longevity. And by taking control of our exposome, we have the power to prevent and reverse chronic disease.

“We have been led to believe that our genes determine the character of our lives, yet new research surprisingly reveals that it is the character of our lives that controls our genes. Rather than being victims of our heredity, we are actually masters of our genome.”

– Bruce Lipton, author of “The Biology of Belief”

Indeed, several studies have found that epigenetic changes are not permanent. One study found that supplementing the diet of mice with methyl donors like vitamin B12 reversed the negative epigenetic alterations caused by poor maternal care.14 Another study found that the natural bioactive compound berberine was able to reverse the epigenetic changes and ameliorate fatty liver disease caused by a poor diet.15

 

How to optimize your exposome and epigenome

We, too, can alter our epigenetics, and our future health as a result. In less than ten years, we’ll likely have affordable technology to measure and track changes in our epigenomes in real-time. Until then, here are several evidence-based ways to optimize your exposome and reduce your risk of chronic disease:

  • Eat a nutrient-dense diet that is appropriate for humans. Make sure that you consume plenty of folate, choline, and vitamin B12, which are important for regulating gene expression.
  • Get plenty of low-level physical activity interspersed with higher intensity exercise. Through epigenetic regulation, exercise has been shown to increase expression of brain-derived neurotrophic factor (BDNF), which stimulates neurogenesis and synapse formation.16
  • Avoid environmental toxins. Exposure to synthetic chemicals or heavy metals has epigenetic consequences. For instance, Bisphenol A, phthalates, arsenic, and mercury have all been shown to negatively impact gene expression.17–19
  • Get plenty of sleep. Just one night of sleep deprivation has been shown to cause altered expression of clock genes in key metabolic tissues.17
  • Manage stress and make time for play. One study found that environmental enrichment was able to reverse the negative epigenetic changes that resulted from prenatal stress.21
  • Support your microbiome. Having your microbiome sequenced can often be more valuable than having whole genome sequencing, as 99% of the genes in your body are microbial and the microbiota heavily influences host epigenetics. For example, when bacteria ferment fiber, they produce a metabolite called butyrate, an incredibly potent epigenetic activator of anti-inflammatory genes.22
  • Look for potential “clues” in your genome. While genes aren’t your destiny, genetic information can still be useful to provide “clues” as to what part of your exposome might be important. For example, my raw genome data revealed a PEMT mutation, which suggested that I might benefit from supplemental choline.23

How will you hack your exposome? Let me know in the comments and be sure to subscribe below!

If you want help interpreting your genetic results or optimizing your epigenome, you can also check out my health coaching services and get a free first consultation.

 

Sources:

  1. The Cost of Sequencing a Human Genome. National Human Genome Research Institute (NHGRI) Available at: https://www.genome.gov/27565109/The-Cost-of-Sequencing-a-Human-Genome. (Accessed: 1st November 2017)
  2. Hong, X. et al. Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth. Nat Commun 8, 15608 (2017).
  3. Takahashi, Y. et al. Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14. Cancer Sci. 108, 2239–2247 (2017).
  4. Peng, C. et al. Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer. Calcif Tissue Int 101, 489–500 (2017).
  5. Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47, 979–986 (2015).
  6. Castillo-Fernandez, J. E., Spector, T. D. & Bell, J. T. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med 6, (2014).
  7. Rappaport, S. M. Genetic Factors Are Not the Major Causes of Chronic Diseases. PLoS One 11, (2016).
  8. Ballestar, E. Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol 39, 30–41 (2010).
  9. Rakyan, V. K. et al. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 7, e1002300 (2011).
  10. Salam, M. T., Zhang, Y. & Begum, K. Epigenetics and childhood asthma: current evidence and future research directions. Epigenomics 4, 415–429 (2012).
  11. Sanchez-Mut, J. V. et al. DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain 136, 3018–3027 (2013).
  12. Masliah, E., Dumaop, W., Galasko, D. & Desplats, P. Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics 8, 1030–1038 (2013).
  13. Wild, C. P. Complementing the genome with an ‘exposome’: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev. 14, 1847–1850 (2005).
  14. Weaver, I. C. G. et al. Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life. J. Neurosci. 25, 11045–11054 (2005).
  15. Chang, X. et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res 51, 2504–2515 (2010).
  16. Gomez-Pinilla, F., Zhuang, Y., Feng, J., Ying, Z. & Fan, G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. European Journal of Neuroscience 33, 383–390 (2011).
  17. Singh, S. & Li, S. S.-L. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates. International Journal of Molecular Sciences 13, 10143–10153 (2012).
  18. Ren, X. et al. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ. Health Perspect. 119, 11–19 (2011).
  19. Onishchenko, N., Karpova, N., Sabri, F., Castrén, E. & Ceccatelli, S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J. Neurochem. 106, 1378–1387 (2008).
  20. Cedernaes, J. et al. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men. J Clin Endocrinol Metab 100, E1255–E1261 (2015).
  21. Morley-Fletcher, S., Rea, M., Maccari, S. & Laviola, G. Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats. European Journal of Neuroscience 18, 3367–3374 (2003).
  22. Berni Canani, R., Di Costanzo, M. & Leone, L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics 4, 4 (2012).
  23. da Costa, K.-A. et al. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 20, 1336–1344 (2006).

 

By |2018-02-21T16:17:16+00:00November 7th, 2017|