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Posts Tagged ‘Gene-Environment’

The Sports Gene (GxE interactions)

Posted in ACTN3, Uncategorized, tagged , , , on September 1, 2013| Leave a Comment »

rg3genes

Have you read The Sports Gene? Maybe you are wondering if your child might be the next Lionel Messi? Or maybe you’re wondering why you were always picked last for kickball? Was it the genes? the practice? or a combination of the two?

We all know kids who seem to have been born with a baseball bat or tennis racquet in their hands. Tall kids, strong kids, fast kids and kids with great hand-eye-coordination. As far back as 1978, the German Tennis Federation had identified 9-year old Steffi Graf as a top recruit based upon her lung capacity, ability to sustain concentration, running speed and her competitive desire. Other kids discover late in life that they have a genetic gift. On a whim, Donald Thomas leaped for his first EVER high jump in 2006 and promptly won the World Championships in 2007.  Chrissie Wellington (world tri-athelete champion) also accidentally discovered her genetic gift late in life (outpacing sherpas on her bicycle while vacationing in Nepal).

As described by David Epstein, the 1996 Olympic games in Atlanta, saw 7 women out of the 3,387 competitors carrying the Y-chromosome-linked SRY gene. 21-hydroxylase deficiency also causes the overproduction of testosterone and is over-represented among top female athletes. The GIANT research consortium has discovered hundreds of “sports genes”, such the rs9930506 SNP in the FTO gene, that contribute to body shape and size. Even more numerous are the complex genetics of height where each genetic variant adds a mere 2-6 millimeters toward NBA stardom. Elite sprinters are more likely to carry 2 functional variants of the fast-muscle-twitch ACTN3 gene. Lastly, an extended network of genes associated with muscle development can – when artificially overexpressed – induce muscle growth: insulin-like growth factor-I (IGF-I), growth hormone (GH), erythropoietin, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and myostatin blockers, such as follistatin.

Sports genes. Few of us are born with them (I was luckily born with the non-obese TT genotype at rs9930506 in the FTO gene, but alas, this allele is associated with a lower response to exercise). Fewer still might be intent upon purchasing a genetic endowment via the taboo art of sports gene doping, especially if they carry the right UGT2B17, CYP17 and PDE7B genotypes. Most of us, however, would just like to maximize our paltry genetic endowments the old fashioned way.

Practice.

Justin Durant of the Sports Science Institute of South Africa is quoted, “I’ve never seen a boy who was slow become fast” but how about late-blooming middle distance runner Jim Ryun whose practice regimen carried him from 21rst on his Wichita East track squad (in 10th grade) to an Olympian and 1-mile world record holder just a single year later? Epstein explores how each of us has an inherent genetic endowment for “trainability” ie. the extent to which our bodies and abilities respond to training. And yes, here too, molecular genetics researchers have identified more “sports genes” in a so-called training responsive transcriptome consisting of genes, including RUNX1, SOX9 and PAX3 whose expression is associated with exercise-dependent muscle growth and CREB1 whose expression is associated with improvements in heart rate and blood pressure.

Sports crazed parents should take note. Your child is probably totally average. Probably like self-described “totally average guy” Dan McLaughlin, who has slogged some 5,500+ hours into his personal experimental journey of “deliberate practice” hoping to land a spot on the PGA tournament by the time he reaches his 10,000th hour of practice. Will he make it? Or will he discover the oft-misconstrued “10,000 hour rule” is more like 4,000 for some and 40,000 hours for others. We wish Dan the best of luck on his quest, but also wish parents to use their children’s precious 10,000 hours for reading, writing, mathing and playing sports for fun rather than trying to attain an NCAA scholarship through mastery of a niche sport.

Will genetic counselors soon be found in pro sport locker rooms or at your local fantasy league draft party? Doubtful, but in 2005, according to Epstein, the Manly Sea Eagles of Australia’s National Rugby League became the first pro sports team to admit that it was genotyping players at ACTN3 and training them differently based on their genotypes.

I loved reading The Sports Gene! Have you ever noticed that NOBODY wants to read a blog or talk about genetics and medical illness, while EVERYBODY loves to talk about sports? Find me a graduate student who can understand (and stay awake while reading) medical GxE research and I will find 1,000 parents who are obsessed with finding the perfect sporting niche and coach for their child.

Whether it be medical treatment or athletic training, a good doctor/coach will seek to optimally match the patient/player’s genetic endowment with treatment/training. The Sports Gene by David Epstein is thus a wonderfully fun and timely playground for readers to explore the complexities of personal genomes and GxE interactions!

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When genes don’t matter, except when they do … a lot

Posted in Uncategorized, tagged , on April 16, 2013| Leave a Comment »

ntbd

Studies on adopted children raised by parents in hostile marriages: show (obviously) that frustration and anger begets frustration and anger … irrespective of genes.

“Although there was no direct association between birth mother anger/frustration and toddler anger/frustration, as noted above, birth mother anger/frustration significantly moderated the relation between adoptive parent marital hostility and later toddler anger/frustration. This genetic moderation is consistent with the premise that children whose birth mothers report higher levels of anger/frustration inherit an emotional lability, making them more susceptible to the negative impact of marital hostility.”

But, for an unfortunate few … the doubly unfortunate experience of having an “inherited emotional lability” while being raised in an emotionally harsh environment, can mean a lifetime of emotional anguish, stress-related-physical suffering and falling through the cracks of society.

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6p21-22 linkage seems to confirm role of immune response in mental illness

Posted in MHC loci, tagged , , , , , , , , , on August 7, 2009| 1 Comment »

Antigen presentation stimulates T cells to bec...
Image via Wikipedia

Its not often that Nature magazine publishes a triple-back-to-back-to-back, so take note if you’re interested in the genetics of mental illness. The 3 papers – [doi:10.1038/nature08185] involving 3,322 individuals with schizophrenia and 3,587 controls, [doi:10.1038/nature08186] 4,999 cases and 15,555 controls and [doi:10.1038/nature08192] 8,008 cases and 19,077 controls – are as massive and powerful as any genome-wide effort to-date.  The results?  Overall a common result showing linkage to the major histocompatibility complex or so-called ‘MHC genes’ located on chromosome 6.  What to these genes do? and what’s the relevence to mental illness?

Here’s a quickie immunology primer on the biological function of the major histocompatibility genes.  They encode proteins whose molecular function is display short peptides on the surface of aptly named antigen presenting cells in the immune system (think of your hand as an MHC protein holding onto an apple (the short peptide) and holding it out or presenting it to someone (an Helper T-Cell).  This act of “presentation” is done so that the Helper T-Cells can determine whether such peptides are “self” or “non-self”.  If such displayed peptides are non-self (such as a virus, endotoxin or bacterium), then the helper T-Cells will sound the alarm and initiate a T- or B-Cell based immune response aimed specifically at the offending invader.  The movies below show the MHC proteins in their place displaying antigen peptides on the cell surface for binding with a helper T-Cell.


So, what does this have to do with mental illness? Although there are other non-immunological genes interspersed among the MHC genes, there is good reason to begin to explore the role of external infection and early development.  The authors of one paper note that,  “Schizophrenia patients are more likely, compared to the general population, to have been born in the winter or the spring. Although infections such as influenza and measles have been proposed as a possible mechanism for this distortion, a clear association between infectious agents and schizophrenia has not been demonstrated.”

The more we know, the more we don’t know.  Hopefully more early environment data will be analyzed.

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Growin’ up in da (rhesus monkey) ‘hood protects against MAOA ‘low’lifes

Posted in MAOA, Uncategorized, tagged , on May 5, 2009| Leave a Comment »

Rhesus Monkeys
Image by Ginger Me via Flickr

As I and many other 23andMe participants begin to confront our genetic innards, we will likely ask whether any of the information is predictive.  Can we expect to read-off our genomic information and say, “I have risk for this, this, and this, and so I’ll change my life to compensate ?”  Certainly, in the area of mental health, there are genetic variants that confer bits of risk toward anxiety, depression, cognitive decline etc., but does the raw genomic information – alone – form a basis for diagnosis and proscriptive change?  In most cases, NO.  Rather, the genome is not unlike a plant seed, that will produce full leafy greens in rich soil, but merely a few buds in poor soil.

A great example of this can be seen in the recent paper, “What is an “Adverse” Environment? Interactions of Rearing Experiences and MAOA Genotype in Rhesus Monkeys” by Karere er al. [doi: 10.1016/j.biopsych.2008.11.004].  In this paper, they compared the emotional development of rhesus monkey infants (n=473) who carry different versions of an MAOA promoter polymorphism – so-called ‘low’ vs. ‘high’ transcriptional level alleles – and also who were reared in different social contexts.  Some of the existing literature on MAOA-environment interactions suggests that abuse or neglect during childhood predisposes individuals who carry the ‘low’ allele (this allele leads to less MAOA protein and less catabolism of 5HT and DA).  In this study, the environment was varied according to numbers of social companions and physical size of the neighborhood – (i) a field enclosure with up to 150 mixed adults & children, (ii) corncrib enclosure with 1 adult male, 2-5 females and various child playmates, (iii) mother-only small enclosure, and (iv) no-mother nursury rearing.

Which environment led to the emotional reactivity (anxiety, aggression etc.) that has been previously associated with the MAOA ‘low’ allele?  Interestingly, it was not the wild & wooly ‘field enclosure’ where infants can interact in a rich, species-typical manner.  Rather, it was the MAOA ‘low’ genotypic infants raised in the smaller groups who showed more signs of emotional reactivity, with cage-mother-only-rearing being the most extreme group.  The authors note that this finding may alter our expectations about what type of environment is optimal vs. adverse and suggest that in the smaller enclosures, the relative isolation underlies the development of anxiety.

From a more general perspective, this study raises questions about how we – humans – should interpret our genomic information.  What environmental conditions enhance or protect us from the potential genetic risk we carry?  How did my early rearing interact with my MAOA allele?  Something to discuss on Mother’s Day.

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