Feeds:
Posts
Comments

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!

GTFO

rage1

Genome discounts

liqorsto

Sign on the window reads, “10% off for rs1800497 TT“ … on account of the way their DRD2 receptors seem to be less responsive … which, naturally, makes them prone to needing to drink (buy) more to feel the same pleasure as CC people. It’s just the free market at work right?

Buh bye DSM

BeFunky_OldPhoto_12

Have you ever read the DSM and thought you had EVERYTHING? Me too.

And that, sort of,  has always been a big problem … that it is really hard to separate the normal experience of anguish and suffering as part of our everyday mental and emotional lives from what is labelled a “disorder”. At the same time, however, patients, doctors and payors need some type of common reference so as to keep the diagnosis and treatment of mental suffering in-line with the way other medical illnesses are handled. So, everyone (in psychiatry, at least) knows the DSM will always be highly flawed and yet also highly necessary … so, you know, just try and live with it … but don’t expect, for a moment, to search for and find discrete genetic variants that correspond to DSM categories of mental disorders. No … because the DSM categories do not correspond well to the underlying biology of the CNS … the DSM does not “cut nature at its joints” so to speak.

Russ Poldrack provides a glimpse into what the future of diagnosing mental illness might look like using slightly more objective, quantifiable and biologically relevant measures of the brain’s physiological processes.

Also, I stumbled onto an awesome read about the creation of DSM-5 entitled, The Book of Woe

The overall thrust of the manual [DSM-5], the BPS complained, was to identify the source of psychological suffering “as located within individuals” rather than in their “relational context,” and to overlook the “undeniable social causation of many such problems.”  The APA could hardly deny any of this. As Regier had told the consumer groups on the conference call, the manual’s new organizational structure was designed to reflect “what we’ve learned about the brain, behavior, and genetics during the past two decades.” It doesn’t get much more “within the individual” and outside the “relational context” than that. (p. 239)

“Dereification is just as dumb as reinfication,” he [Allen Frances] told me. “A construct is just a construct – not to be worshiped and not to be denigrated.” Psychiatry, he was saying, has to live in the tension between the desire for certainty about the nature of our suffering and the impossibility of understanding it (or ourselves) completely. A DSM that tries to end this tension by turning itself into a living document was bound to collapse into chaos; that was the cardinal error of the incompetent DSM-5 regime. (p. 279)

“What [Dr. Thomas] Insel [Director of NIMH] heard “over and over again” on his tour was that psychiatrists were tired of being trapped by the DSM. “We are so embedded in this structure,” he told me. He and his colleagues had spent so much time diagnosing mental disorders that “we actually believe they are real. But there’s no reality. These are just constructs. There’s no reality to schizophrenia and depression.” Indeed, Insel said, “we might have to stop using terms like depression and schizophrenia, because they are getting in our way, confusing things.” Thirty years after Spitzer burned down DSM-II and built the DSM-III in its ashes, psychiatry might once again have to “just sort of start over.”” (p.340)

Yikes! after reading The Book of Woe, DSM-5 sounds, um, totally wack … if not a tool flagrantly designed to further commodify human suffering for the benefit of a medico-industrial complex. NIMH Director Thomas Insel’s recent announcement that, “NIMH will be re-orienting its research away from DSM categories.” suggests a future where diagnosis will based on biological measures and treatments are directed toward specific circuits.

Treatment for specific circuit dynamics sounds very promising. However, I thought Dr. Allen Frances, as quoted in The Book of Woe made a great point (p.346) that, “The trick is to develop a healing relationship, to care for the person not just the disorder, to diagnose and treat cautiously, and to see the healthy part of the person not just the sick.”

* Maybe that is the hope of this blog also … to take out and explore the intricate biological & molecular parts … but also to try and place them back into their original evolutionary, living, breathing, copulating (or more often the case of just thinking about copulating) “whole” human being.

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.

rs806377 and rs806380

groom

Learning to read emotions and faces is important for our well-being.  For some of us, the act of gazing into another person’s eyes is innately rewarding … especially if they are smiling.  New mothers and their infants can be found locked in each others smiling countenance … thus strengthening the developing neural pathways upon which the infant’s future social skills will grow.

One component of these neural pathways is the CNR1 gene expressed in the striatum and other brain regions that process rewarding and positively-reinforcing stimuli.  For most of us, a happy smiling face is positively rewarding … moreso with certain CNR1 genotypes.

From Drs. Baron-Cohen and Chakrabarti:

“A comparison of these results with those from our earlier fMRI study reveals that for the SNP rs806377, the allelic group (CC) associated with the highest striatal response is also associated with the longest gaze duration for happy faces. For rs806380, the allelic group associated with the highest striatal response (GG) is also associated with the longest gaze duration for happy faces.”

My 23andMe profile shows both the long-gaze CC and GG genotypes for rs806377 and rs806380.  Mmmmkay … I guess this would be a good time to apologize to all the girls I inappropriately stared at in the cafeteria back in college … even though you weren’t usually smiling back at me.  I guess my CNR1 and striatum were pretty overactive.

tumblr_lfbl0vftbD1qc38e9o1_400

The above images are eigenfaces … which are statistically distilled basic components of human faces … from which ANY human face can be reconstructed as a combination of the above basic components.  It’s a great mathematical trick – particularly if you’re into the whole mass surveillance and electronic police state thing.

If you are more into the whole, helping people and medical care thing, check out the global consortia at ENIGMA who have been carrying out massive genetic and brain scanning studies – like this one involving 437,607 SNPs in 31,622 voxels in 731 subjects using their new method, vGeneWAS, to study Alzheimer’s Disease:

“We hypothesized that vGeneWAS would, in some situations, have greater power to detect associations than existing SNP-based methods. One such situation might be when a gene contains many loci with weak individual effects. In addition, we expected that vGeneWAS would have greater overall power than mass SNP-based methods, like vGWAS, because of the drastic reduction in the effective number of statistical tests performed.”

The vGeneWAS method relies on the calculation of “eigenSNPs” which are eigenvectors that describe a matrix of n subjects by m SNPs in an individual gene (an n-x-m matrix of 1’s,0’s,-1’s for aa, aA, AA genotypes).  EigenSNPs are sort of like eigenfaces insofar as eigenSNPs (which are not actual SNPs) capture the majority of variance, or the basic essence of an individual gene … but seriously, you should read the original article ’cause every stats test I ever took totally punched me in the face.

In any case, the eigenSNP-by-voxel method pulled out some legit results such as rs2373115 (where the G-allele confers risk) in the GAB2 gene  which has repeatedly been implicated in the risk of age-related late-onset Alzheimer’s Disease (in folks who carry ApoE4  rs429358(C) alleles).  The authors found that the genetic risk of AD conferred by GAB2 may arise by way of GAB2’s effect on brain structure in the periventricular areas, which have been known to be among the first brain regions to show AD-related changes (time-lapse movie of AD tissue loss in the brain).

Picture 2