DNA and You

Steven Pinker of the PGP in the NY Times Magazine

Matt Mealiffe, M.D. — Sat, 10 Jan 2009 12:41:17 -0800

Very interesting article by Steven Pinker of the Personal Genome Project in the NY Times Magazine. Check it out here.

Is It Heritable? Twin Study Evidence Suggests Eyeball (aka Intraocular) Pressure is Substantially Affected by Genetics

Matt Mealiffe, M.D. — Tue, 02 Dec 2008 23:14:30 -0800

As I've previously mentioned, twin studies allow an estimation of the heritability of a trait by comparing the degree of concordance in a given phenotype between MZ (identical) twins and DZ (fraternal) twins.

I recently came across a fascinating study looking at the heritability of intraocular pressure - that is -the pressure on the inside of the eyeball that ophthalmologists and optometrists measure when screening for glaucoma. Carbonaro and colleagues, from the Twin Research and Genetic Epidemiology Unit at King's College London School of Medicine, performed a classical twin study to estimate intraocular pressure (IOP) heritability¹. Although there was some modest variability in the heritability estimates depending on which of 3 instruments was utilized to measure IOP, the results suggested that genetic factors explain about 62 percent of the variation in IOP, with individual environmental factors and/or stochastic factors accounting for the remainder.

62 percent is impressively high, but of course does not tell us anything about the genetic architecture of the trait. Although some progress has been made in understanding the genetics of congenital glaucoma, we have much further to go with adult glaucoma/IOP elevation. Despite the existence of a few clues^2-4, much work remains to be done.

Photo: By ninjapoodles via Creative Commons.

Cited References

1. Carbonaro F, Andrew T, Mackey DA, Spector TD, Hammond CJ. Heritability of intraocular pressure: a classical twin study. Br J Ophthalmol 92:1125-8, 2008.

2. Duggal P et al. Identification of novel genetic loci for intraocular pressure: a genomewide scan of the Beaver Dam Eye Study. Arch Ophthalmol 125:74-9, 2007.

3. Wiggs JL et al. Genome-wide scan for adult onset primary open angle glaucoma. Hum Mol Genet 9:1109-17, 2000.

4. Nemesure B et al. A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma. Hum Genet 112:600-9, 2003.

If You Think Wired Is a Good Place to Go for Medical Advice, Think Again...

Matt Mealiffe, M.D. — Tue, 08 Jul 2008 22:33:59 -0700

Andrew Yates at Think Gene wrote today about the new Wired Wiki home genomics how-to guide, "Check Yourself for Genomic Abnormalities." Check out Andrew's post for a great discussion of the maturity, or, rather, the lack thereof, of the personal genomics market.

Something caught my eye though as I read through "Check Yourself for Genomic Abnormalities" at the Wired Wiki site. The wiki post describes several options for "checking yourself for genomic abnormalities": 1) Visit a Genetic Counselor; 2) Scan Your Whole Genome; and 3) Perform Lab Tests at Home.

Interestingly, the author(s), who otherwise did an ok job of briefly explaining what genetic counselors do, utilized consideration of a diagnosis of celiac sprue as an example of a situation in which someone would want to see a genetic counselor rather than "scanning their whole genome" or "performing lab tests at home."

I think the world of Wired, but in case it is not clear to the early adopters out there...

Wired is probably not where you want to get your medical advice.

Celiac disease (aka gluten-sensitive enteropathy or non-tropical sprue), the condition mentioned in the hypothetical scenario, is diagnosed via a blood antibody test and small intestinal biopsies. Thus, rather than seeing your local genetic counselor if you think you might have CD, you would do well to discuss it with your primary care doctor and a gastroenterologist.

The wiki writer's confusion likely stems from the fact that genetic factors do play a role in risk for Celiac disease; however, the genetics are complex, and the genes involved are not deterministic. For example, risk of Celiac disease is higher if you have certain forms ("alleles") of HLA genes. About 30% of the population has one of the Celiac disease-associated HLA alleles; however, only 3% of individuals with the Celiac disease-associated allele develop CD.

Music and Your Genes: One Step Closer to Understanding the Biological Basis of Musical Ability

Matt Mealiffe, M.D. — Thu, 03 Jul 2008 07:39:34 -0700

We've all come across certain people who seem to have a particularly high ability to play and/or appreciate music. As a geneticist, my assumption has always been that this is inherent and heritable to some degree. Nevertheless, it could certainly be argued that it is environmental.

The literature provides some support for the concept that musical ability is genetic. For example, musical talent has been noted to cluster in some families. Additionally, the ability to identify pitch in the absence of a reference pitch clusters in families, as well. Conversely, tone deafness, also known as congenital amusia, also seems to be genetic on the basis of strong familial clustering. Lastly, in a formal study of pitch recognition in twins, the heritability of scores on the so-called Distorted Tunes Test were estimated to be more than 70%.

Now, a Finnish research group has demonstrated that it is highly likely that a gene on chromosome 4 (located in the vicinity of chromosome band 4q22) influences musical aptitude. They utilized three different measures of musical aptitude in coming to this conclusion and performed a "genome-wide linkage test." This study has narrowed the region containing the gene to a segment of the chromosome containing ~50 genes, so further studies will be necessary to find the precise genetic change influencing musical aptitude in these families. The authors also noted other regions of the genome in which there was suggestive linkage, suggesting that musical aptitude is likely to be affected by multiple genes. It will be interesting to watch as these are hopefully identified in future studies.

Reference

K Pulli et al. Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22. Journal of Medical Genetics 45: 451-6, 2008.

Is it heritable? Twin study evidence suggests acne can be inherited

Matt Mealiffe, M.D. — Wed, 02 Jul 2008 00:08:40 -0700

Have you ever wondered whether acne risk can be inherited? Twin studies can shed light on this question.

In a previous post, I discussed twin studies which are the genetic gold standard to determine whether the liklihood of developing a given medical condition (or trait) is subject to heritable (i.e., genetic) influences. The concept is fairly simple: Identical twins share essentially 100% of their genetic material while fraternal twins share 50%. If genetics plays a strong role in risk for a disease, when twin pairs in which one member has the disease are studied, both twins will have the same disease in a larger percentage of the identical twin pairs as compared to the fraternal twin pairs.

One study applied this concept to the study of acne. The results were clear: in this study, approximately 80% of the degree to which acne severity varied was due to genetic effects.

Although the underlying causative genes are not known, the fact that genetics plays such a large role in the development of acne suggests that future efforts to find the underlying genes are likely to reveal new drug targets.

High Throughput Sequencing, Moore's Law, The Next Generation, and Storage Options

Matt Mealiffe, M.D. — Tue, 01 Jul 2008 22:44:25 -0700

It will be interesting to see if DNA sequencing technology continues to follow a Moore's law-like trajectory over the coming decades. Clearly, next generation technologies are going to have a massive impact both in the research setting and on medical resequencing.

Alexis Madrigal at Wired Science wrote a nice piece on the technological advances leading to the current generation of high-throughput sequencers and also the next generation: Pacific Biosciences and Helicos.

Also notable is a post from the always excellent Daniel MacArthur at Genetic Future on options for storage of personal genome sequences.

Voices of the Infertile in the NY Times

Matt Mealiffe, M.D. — Tue, 24 Jun 2008 01:08:51 -0700

Infertility, which in some cases can have a genetic cause, is a challenging obstacle for many couples. A recent article by Karen Barrow, in the NY Times, focuses on the challenges faced by couples unable to conceive.

An interactive feature associated with the article features the voices of several of women interviewed.

Rett Syndrome on Fox Show: "So You Think You Can Dance"

Matt Mealiffe, M.D. — Tue, 24 Jun 2008 00:50:15 -0700

Tara Parker-Pope of the NY Times writes about an episode of the Fox reality show, "So You Think You Can Dance," in which Rett syndrome was featured.

For more on Rett Syndrome:

Rett Syndrome (MECP2-Related Disorders) GeneReview

International Rett Syndrome Foundation

Mandatory Waistline Measurement in Japan: Good Public Health Social Policy? Or Genetic Discrimination Against Fat People?

Matt Mealiffe, M.D. — Sat, 14 Jun 2008 08:25:24 -0700

The NY Times has a really interesting piece on a new policy of mandatory waistline measurement in Japan. With a goal of improving the public health, the government has established a state prescribed limit on male waistlines of 33.5 inches along with a limit of 35.4 inches for women...

No...I'm really not kidding.

Companies and local governments will apparently be required - under this new national law - to measure waistlines of those 40-74 years old during annual checkups. Apparently, those not meeting the country's standard will be given dieting guidance if they do not meet the standard and do not lose the weight over 3 months (with subsequent escalation of the scrutiny and advice if folks are still too rotund at 6 months).

Interestingly, the Japanese government intends to impose monetary penalties on entities (local governments and companies that fail to meet specific targets).

Although I am sure that the Japanese government has good intentions, this is a very interesting policy in light of the fact that obesity is a trait that can only be partially modified by behavioral change. In other words, it is clear that obesity risk is to some extent a heritable trait, determined to some extent by one's genetic background, that can be difficult for some individuals to overcome.

Although this is an interesting and aggressive experiment aimed at reducing healthcare costs, it has the potential to result in further stigmatization of those affected by the obesity epidemic (something that is, no doubt, intended by the rule since it may result in public health benefits). By imposing penalties on local governments and companies, the government is avoiding the appearance of discriminating against those with generous waistlines; however, this will create tremendous incentives on these entities to exert considerable pressure on individuals whose waists are over the limits.

In sum, it's a bold social policy. It may help with healthcare costs in the long-run, but is it genetic discrimination?

What do you think?

COPD and Your Genes: New Study of Familial Risks for Chronic Obstructive Pulmonary Disease

Matt Mealiffe, M.D. — Fri, 13 Jun 2008 22:41:22 -0700

Yesterday, at Cancer and Your Genes, I mentioned an interesting study assessing the degree to which survival in prostate cancer seems to run within families (and therefore may be genetic). Some of the same authors, including Kari Hemminki, the lead author, also have a paper in the May 2008 issue of the Journal of Epidemiology and Community Health that assesses familial risks for chronic obstructive pulmonary disease (COPD) amongst siblings in Sweden.

The results basically showed that siblings of individuals with COPD had much higher risks of COPD themselves (Standardized Incidence Ratio [SIR] = ~4.6) as compared to spouses of individuals with COPD (SIR = ~1.6). The fact that the SIR was much higher for sibling pairs than for spouses is consistent with genetics underlying at least some familial susceptibility to this disabling lung disease.

Although there is a rare familial cause of COPD (alpha-antitrypsin deficiency), it seems unlikely that this would account for a significant fraction of the familial effect. It will be interesting to see what we learn in the future about other genes underlying COPD risk--and also the extent to which they interact with a known environmental risk factor for this disease, smoking, which itself has a heritable component. Very complicated!