… but not like this. Try openSNP.
Posts Tagged ‘Personalized medicine’
when you realize that the genetic risk of that allele you carry was calculated using a small population from south-western-upper-middle-eurasia-stan … and doesn’t really apply to your individual situation.
Perhaps just a little bit. One Law Professor’s experience.
“As it happens, … It turned out that I had a genetic variant that implied a moderately increased risk of meningioma, the second most common type of brain tumor.
The information came a little late to be useful. Last summer, … found me half conscious on the floor. The diagnosis at the local hospital was meningioma, a benign (i.e. non-cancerous) tumor inside my skull but fortunately outside my brain.”
Check out the Interpretome! developed by students and staff at Stanford University.
- I have 17 European alleles and 3 East Asian alleles … the genetic proof is in … white boys can’t jump.
- I have 17 out of 32 Type 2 Diabetes risk alleles … put down those carbs now … and 19 out of 30 Coronary Artery Disease risk alleles … and go for a jog.
- I have a combined Risk of Narcolepsy: 2.92 … but the score jumps to 85 with an issue of GENETICS in my hand.
- I’m not exactly on the leading edge of human evolution … a 72/110 of positive selection score.
- I’d better start saving for a long-ass retirement … probability of extreme longevity: 78.2
“For example, have you thought about epigenetic effects that might be environmentally induced and can be transmitted across multiple subsequent generations? Genotypes of individuals in previous generations might even be a better predictor of phenotype than an individual’s own genotype.”
“I know that Copy-Number Polymorphic (CNP) duplications are highly variable among individual and are considered inaccessible by most existing genotyping and sequencing technologies, but I’m still getting my genome sequenced anyway.”
“Can you please help Eric understand that rare variants and large variants (deletions, duplications and inversions) are individually rare, but collectively common in the human population might account for much more of heritability than common variation. Nothing is known about these rare variants!”
–real science here.
The genetic profiling results show that your son carries 2 copies of the so-called “short” allele at the serotonin transporter linked polymorphic region (5-HTTLPR) and also 2 copies of the T allele of the G-703T polymorphism (rs4570625) in the tryptophan hydroxylase-2 (TPH2) gene.
Some studies find correlations between this genotype and higher amygdala activity – which, in turn – has been correlated with a number of anxiety-related traits and disorders.
In short, you may wish to expect that your son may grow up to be slightly more shy, bashful, diffident, inhibited, reticent, shrinking, hesitant, timid, apprehensive, nervous, wary, demure, coy, blushing, self-effacing, apprehensive, fearful, faint-hearted, wimpish, mousy, lily-livered, weak-kneed, unsure & doubtful.
Congratulations! He will be a handful to raise as a child but one day make a great scientist, and an even better science blogger.
* thanks fyns for the pic.
Pointer to Daniel MacArthur’s (Genomes Unzipped) post on the recent political grandstanding in consumer genetics.
This blog is more genomes, brains, social entrepreneurship and health 2.0 – than politics. Hopefully the political phase will soon pass and some sensible regulations will preserve the right of consumers to access their genomes, while protecting consumers from scammers.
The one thing I hope does not happen is that the regulatory agencies (they work for us right?) “punt” on the issue and turn the whole consumer genetics ball of wax over to medical doctors and the medical insurance complex. Like many, I am inspired by open-source, open-access, crowd-sourcing, bioinformatic and other open, web-based tools that allow consumers to by-pass the so-called “experts” in news media, finance, health and so many other industries that are being transformed by information technology. The economic benefits for consumers are well documented, and so, a country like the U.S. – economically sinking in a healthcare affordability crisis – might benefit (in the longer run) if it nurtured industries that helped consumers freely and openly ascertain their risks for illness without having to go through the economic choke point of an establishment of medical “experts”.
See health 2.0, Regina Herzlinger’s “Who Killed Health Care?“, Michael E. Porter and Elizabeth Olmsted Teisberg’s “Redefining Health Care: Creating Value-Based Competition on Results“, Andy Kessler’s “The End of Medicine: How Silicon Valley (and Naked Mice) Will Reboot Your Doctor“ and Nobel Prize-winning economist Kenneth Arrow’s classic 1963 essay “Uncertainty and the Welfare Economics of Medical Care“ for some more on this.
Update: The comment stream on Daniel MacArthur’s (Genomes Unzipped) post are chilling. Many of the responders seem to have experience in the direct-to-consumer genetics business, and they don’t sound as optimistic as my (naive) self. Part of one comment:
Seriously, you don’t understand. The DTC testing industry is ALREADY DEAD. In the Wall Street Journal, Shuren declared DTC subject to PMA approval, which costs tens of million of dollars! People are quitting the companies by the droves. 23andMe’s former director of regulatory affairs left for NextBio. VCs have refused to re-up. There will be no Series X+1 financing for an industry with no growth potential.
Posted in Mindfulness, tagged B. K. S. Iyengar, Breathing, Buddism, Central nervous system, Consciousness, dualism, Emotion, Health, Human, India, informatics, Meditation, mindfulness, Mood, Nervous system, Neuron, parasympathetic nervous system, Patañjali, Personalized medicine, philosophy, Religion and Spirituality, Shopping, spirituality, Yoga on June 29, 2010 | Leave a Comment »
Like many folks, I generally feel better ever since I started practicing yoga. Outwardly, my body is (slowly) growing stronger and more flexible and perhaps (hopefully) soon, I’ll even lose a few pounds. However, even if I was to convince myself that looked slimmer (skinny mirrors?), the only way to really know if I’ve lost weight, is to stand on a scale and record my weight each day (darn! no fatness lost so far).
That takes care of the body right – but what about the inner, emotional improvements I might be experiencing? How to measure these?
Here are some mobile- and web-based tools to help one track one’s emotions. Most of these websites, like Moodstats, Track Your Happiness, MoodJam, MoodMill, Finding Optimism and MoodLog seem to function as online diaries which keep a running tab on aspects of ones moods and emotions. Perhaps such tools – if used over long durations – would enable one to verify a shift toward a less anxious and more contented inner feeling? I don’t know.
Perhaps the real proof of “inner” progress would be that I had closed my computer and put away my mobile device and, rather, was outside enjoying the sights and sounds of nature. Perhaps best to avoid mixing yoga and digital distractions.
just a pointer to: Genetic Future’s pointer to the recent article, “Family become first to have DNA sequenced for non-medical reasons“. The father suggests, “it will be ethically improper if you don’t have your children sequenced“.
Posted in Basal Ganglia, Caudate nucleus, DAT, Dopamine, Putamen, Substantia nigra, Subthalamic nucleus, tagged ADHD, Attention-deficit hyperactivity disorder, Basal Ganglia, Brain, Cognition, Development, Frontal lobe, Gene expression, Genetic testing, Genetics, Health, inhibition, Mental disorder, Mental health, Neural network, Personalized medicine, Substantia nigra on March 5, 2010 | 1 Comment »
I have a little boy who loves to run and jump and scream and shout – a lot. And by this, I mean running – at full speed and smashing his head into my gut, jumping – off the couch onto my head, screaming – spontaneous curses and R-rated body parts and bodily functions. I hope you get the idea. Is this normal? or (as I oft imagine) will I soon be sitting across the desk from a school psychologist pitching me the merits of an ADHD diagnosis and medication?
Of course, when it comes to behavior, there is not a distinct line one can cross from normal to abnormal. Human behavior is complex, multi-dimensional and greatly interpreted through the lens of culture. Our present culture is highly saturated by mass-marketing, making it easy to distort a person’s sense of “what’s normal” and create demand for consumer products that folks don’t really need (eg. psychiatric diagnoses? medications?). Anyhow, its tough to know what’s normal. This is an important issue to consider for those (mass-marketing hucksters?) who might be inclined to promote genetic data as “hard evidence” for illness, disorder or abnormality of some sort.
With this in mind, I really enjoyed a recent paper by Stollstorff et al., “Neural response to working memory load varies by dopamine transporter genotype in children” [doi:10.1016/j.neuroimage.2009.12.104] who asked how the brains of healthy children functioned, even though they carry a genotype that has been widely associated with the risk of ADHD. Healthy children who carry genetic risk for ADHD. Hmm, might this be my boy?
The researchers looked at a 9- vs. 10-repeat VNTR polymorphism in the 3′-UTR of the dopamine transporter gene (DAT1). This gene – which encodes the very protein that is targeted by so many ADHD medications – influences the re-uptake of dopamine from the synaptic cleft. In the case of 10/10 genotypes, it seems that DAT1 is more highly expressed, thus leading to more re-uptake and hence less dopamine in the synaptic cleft. Generally, dopamine is needed to enhance the signal/noise of neurotransmission, so – at the end of the day – the 10/10 genotype is considered less optimal than the 9/9-repeat genotype. As noted by the researchers, the ADHD literature shows that the 10-repeat allele, not the 9-repeat, is most often associated with ADHD.
The research team asked these healthy children (typically developing children between 7 and 12 years of age) to perform a so-called N-back task which requires that children remember words that are presented to them one-at-a-time. Each time a new word is presented, the children had to decide whether that word was the same as the previous word (1-back) or the previous, previous word (2-back). Its a maddening task and places an extreme demand on neural circuits involved in active maintenance of information (frontal cortex) as well as inhibition of irrelevant information that occurs during updating (basal ganglia circuits).
As the DAT1 protein is widely expressed in the basal ganglia, the research team asked where in the brain was variation in the DAT1 (9- vs. 10-repeat) associated with neural activity? and where was there a further difference between 1-back and 2-back? Indeed, the team finds that brain activity in many regions of the basal ganglia (caudate, putamen, substantia nigra & subthalamic nucleus) were associated with genetic variation in DAT1. Neat! the gene may be exerting an influence on brain function (and behavior) in healthy children, even though they do not carry a diagnosis. Certainly, genes are not destiny, even though they do influence brain and behavior.
What was cooler to me though, is the way the investigators examined the role of genetic variation in the 1-back (easy or low load condition) vs. 2-back (harder, high-load condition) tasks. Their data shows that there was less of an effect of genotype on brain activation in the easy tasks. Rather, only when the task was hard, did it become clear that the basal ganglia in the 10/10 carriers was lacking the necessary brain activation needed to perform the more difficult task. Thus, the investigators reveal that the genetic risk may not be immediately apparent under conditions where heavy “loads” or demands are not placed on the brain. Cognitive load matters when interpreting genetic data!
This result made me think that genes in the brain might be a lot like genes in muscles. Individual differences in muscle strength are not associated with genotype when kids are lifting feathers. Only when kids are actually training and using their muscles, might one start to see that some genetically advantaged kids have muscles that strengthen faster than others. Does this mean there is a “weak muscle gene” – yes, perhaps. But with the proper training regimen, children carrying such a “weak muscle gene” would be able to gain plenty of strength.
I guess its off to the mental and physical gyms for me and my son.
Posted in ADORA2A, DRD2, Uncategorized, tagged 23andMe, Anxiety, Brain, Caffeine, Coffee, Cognition, Disorders, DNA, evolution, Genetic testing, Genetics, Mental disorder, Mental health, panic disorder, Personalized medicine, Psychoactive drug, Starbucks, Stress on March 4, 2010 | Leave a Comment »
If you’re a coffee drinker, you may have noticed the new super-sized portions available at Starbucks. On this note, it may be worth noting that caffeine is a potent psychoactive substance of which – too much – can turn your buzz into a full-blown panic disorder. The Diagnostic and Statistical Manual for psychiatry outlines a number of caffeine-related conditions mostly involving anxieties that can arise when the natural alertness-promoting effects are pushed to extremes. Some researchers have begun to explore the way the genome interacts with caffeine and it is likely that many genetic markers will surface to explain some of the individual differences in caffeine tolerance.
Here’s a great paper, “Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety” [doi: 10.1038/npp.2008.17] wherein polymorphisms in the adenosine A2A receptor (ADORA2A encodes the protein that caffeine binds to and antagonizes) – as well as the dopamine D2 receptor (DRD2 encodes a protein whose downstream signals are normally counteracted by A2A receptors) — show associations with anxiety after the consumption of 150mg of caffeine (about an average cup of coffee – much less than the super-size, super-rich cups that Starbucks sells). The variants, rs5751876 (T-allele), rs2298383 (T-allele) and rs4822492 (G-allele) from the ADORA2A gene as well as rs1110976 (-/G genotype) from the DRD2 gene showed significant increases in anxiety in a test population of 102 otherwise-healthy light-moderate regular coffee drinkers.
My own 23andMe data only provides a drop of information suggesting I’m protected from the anxiety-promoting effects. Nevertheless, I’ll avoid the super-sizes.
rs5751876 (T-allele) C/C – less anxiety
rs2298383 (T-allele) – not covered
rs4822492 (G-allele) – not covered
rs1110976 (-/G genotype) – not covered
Posted in SLC1A1, tagged 23andMe, anti-psychotic, Biology, clozapine, DNA, economics, genetic association, Genetic testing, Glutamate, Health care, medication, Mental disorder, Mental health, obsessive-compulsive, Personalized medicine, side-effect on December 15, 2009 | Leave a Comment »
In their forecast “The World in 2010” special issue, the Economist points to “The looming crisis in human genetics” wherein scientists will reluctantly acknowledge that, even with super-cheap genome sequencing tools, we may not soon understand how genetic variation contributes to complex illness. The argument is a valid one to be sure, but only time will tell.
A paper I read recently, reminded me of the long hard slog ahead in the area of genomics and psychiatric illness. The authors in “Association of the Glutamate Transporter Gene SLC1A1 With Atypical Antipsychotics–Induced Obsessive-compulsive Symptoms” [Kwon et al., (2009) Arch Gen Psychiatry 66(11)] are trying to do something very important. They would like to understand why certain (most) psychiatric medications have adverse side-effects and how to steer patients clear of adverse side-effects. This is because, nowadays, a patient learns via a drawn-out trial-and-error ordeal about which medications he/she can manage the benefits/costs.
Specifically, the authors focused their efforts on so-called obsessive-compulsive symptoms that can arise from treatment with atypical antipsychotic medications. Working from 3 major medical centers (Samsung Medical Center, Seoul National University Hospital and Asan Medical Center) Kwon et al., were able to cobble together a mere 40 patients who display these particular adverse side-effects and matched them with 54 patients based on several demographic and medication-based criteria. Keep in mind that most genetic studies use upwards of 1,000 samples and still – hardly – are able to obtain significant effects.
Nevertheless, the authors note that the glutamate transporter gene (SLC1A1 or EAAC1) is a most logical candidate gene, being a located in a region mapped for obsessive-compulsive disorder risk and also a gene that appears to be down-regulated in response to atypical anti-psychotic treatment (particularly clozapine). A series of statistical association tests for 10 SNPs in this gene reveal that two SNPs (rs2228622 and rs3780412) and a 3-SNP haplotype (the A/C/G haplotype at rs2228622-rs3780413-rs3780412) showed modestly significant association (about 4-fold higher risk) with the adverse symptoms.
To me, this is a very noteworthy finding. A lot of work went into a very important problem – perhaps THE most pressing problem for patients on anti-psychotic medications today – and the results, while only of modest significance, are probably biologically valid. The authors point out that rs2228622 and rs3780412 have previously been associated with OCD in other studies.
But when you compare these modest results (that these authors fought hard to obtain) with the big promises of the genomic era (as noted in the Economist article), well then, the results seem rather diminutive. Will all patients who carry the risk haplotype be steered away from atypical antipsychotics? Will big pharma (the authors of this paper disclose a great many ties to big pharma) support the fragmentation of their blockbuster drug markets into a hundred sub-populations? I doubt it. But some doctors and patients will experiment and continue to explore this avenue of inquiry – and it will take a long time to work out. Better check back in 2020.
Posted in ADH1C, Amygdala, Caudate nucleus, CDH13, GATA4, Striatum, tagged 23andMe, Addiction, Brain, Gene expression, Genetic testing, Mental disorder, Mental health, Personalized medicine, Biology, Genetics, Genome-wide association study, Alcoholism, Alcohol, GWAS on November 16, 2009 | Leave a Comment »
A recent GWAS study identified the 3′ region of the liver- (not brain) expressed PECR gene (rs7590720(G) and rs1344694(T)) on chromosome 2 as a risk factor for alcohol dependency. These results, as reported by Treutlein et al., in “Genome-wide Association Study of Alcohol Dependence” were based on a population of 487 male inpatients and a follow-up re-test in a population of 1024 male inpatients and 996 control participants.
The authors also asked whether lab rats who – given the choice between water-based and ethanol-spiked beverages over the course of 1 year – showed differential gene expression in those rats that were alcohol preferrers vs. alcohol non-preferring rats. Among a total of 542 genes that were found to be differentially expressed in the amygdala and caudate nucleus of alcohol vs. non-alcohol-preferring rat strains, a mere 3 genes – that is the human orthologs of these 3 genes – did also show significant association with alcohol dependency in the human populations. Here are the “rat genes” (ie. human homologs that show differential expression in rats and association with alcohol dependency in humans): rs1614972(C) in the alcohol dehydrogenase 1C (ADH1C) gene, rs13273672(C) in the GATA binding protein 4 (GATA4) gene, and rs11640875(A) in the cadherin 13 (CDH13) gene.
My 23andMe profile gives a mixed AG at rs7590720, and a mixed GT at rs1344694 while I show a mixed CT at rs1614972, CT at rs13273672 and AG at rs11640875. Boooring! a middling heterozygote at all 5 alcohol prefer/dependency loci. Were these the loci for chocolate prefer/dependency I would be a full risk-bearing homozygote.
Science IS fun … props to Francis Collins for going out on a limb for the younger crowd on the Colbert Report.
Even though the data collection technology still outpaces the deeper understanding of the data, we’re learning more and more all the time.
pointer to next week’s conference in Bethesda NIH State-of-the-Science Conference: Family History and Improving Health. From the website, “Family history is also critical to determining who will benefit from genetic testing for both common and rare conditions, and can facilitate interpretation of genetic test results.” You can watch live or later via an archived webcast!
Last summer I took a day to drive to Camden, NJ to attend a free lecture & spit event at the Coriell Institute. Today, I was pleased to find that the data are flowing through their user-friendly web portal. After about 40 minutes of standardized online family, lifestyle & medical history questionnaires, I was able to view my data:
Iron Overload Genetic Variant #1 (HFE rs1800562)
GG – low risk
Type 2 Diabetes – Variant #1 (rs7754840)
CG – medium risk
Prostate Cancer – Variant #1 (rs16901979)
CC – low risk
Coronary Artery Disease – Variant #1 (rs1333049)
GC – low risk
Melanoma Genetic Variant #1 (rs910873)
CC – low risk
These data match my 23andMe results (except for Melanoma Genetic Variant #1 (rs910873) which is not covered by 23andMe) and the online medical education resources for each genetic test are extensive. According to the site, more data and related medical education will be flowing soon.
Glad to have this free, albeit minimal, access to my genome information!
pointer to: Great Q&A on Freakonomics with 23andMe founder Anne Wojcicki. Nice overview of peoples’ concerns and interests in personal genomes.