Preimplantation Genetic Diagnosis (PGD): A Discussion

by Dr. Hsien-Hsien Lei
Posted November 6, 2008 in DNA and Disease

This past April, I participated in a vodcast with Dr. Chris Korey of the College of Charleston and students in his Molecular Biology Lab. We talked about the science and ethics behind direct-to-consumer genetic testing. While I’m not too pleased with the way I looked while heavily pregnant (eek!), we had a great conversation and I was impressed with the students’ enthusiasm and thoughtfulness.

This month, Dr. Misha Angrist is the guest participant and he’s hosting a discussion on preimplantation genetic diagnosis (PGD), selection and disability on his blog, Genomeboy. I hope you’ll join the students in conversation there.

For more information on PGD, please see these previous posts here at Eye on DNA:

• Eye on DNA Podcast Interview: Huntington’s Disease
• Preimplantation Genetic Diagnosis for Early-Onset Alzheimer’s Disease
• Parents Feel Guilty Over Giving Children Bad Genes
• Genetic Testing to Prevent Wrongful Life
• Medical Tourism for Preimplantation Genetic Diagnosis
• IVF Strategies: Cloned Sperm and Preimplantation Genetic Diagnosis

(>> Start a discussion!)

Family History of Disease Scares Parents More Than Genetic Test Results

by Dr. Hsien-Hsien Lei
Posted November 6, 2008 in DNA Testing, DNA and Disease

Should parents purchase direct-to-consumer genetic tests for their under-age children? Joanna Mountain, Senior Director of Research at 23andMe, chose to do so for her two sons and found it to be a positive experience overall (of course!). I have not done so for my two children and haven’t even done so for myself. Just call me chicken.

In a timely study published in the November issue of the Archives of Pediatrics & Adolescent Medicine, researchers at the University of Michigan CS Mott Children’s Hospital staged a hypothetical situation and randomized over 1,300 parents to receive hypothetical genetic risk assessments framed as family history or genetic test results. They found that parents were actually more worried if they had observable, tangible evidence of a family history of disease than if the results were purely based on genetic tests.

So it seems that nothing strikes fear into our hearts more than knowing that a family member is ill and that we may also have inherited an increased susceptibility to the illness. While genes may be floating around in our consciousness, they remain an abstract concept that most of us are not able to include in our daily risk analyses.

NB: Daniel MacArthur at Genetic Future has more on genome scans for the whole family although he considers it mainly from a business perspective than from one as a parents since he isn’t one yet.

via Los Angeles Times

Photo credit: Wellcome Images

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Bioethicist Arthur Caplan Says Corporate Greed Drives Genetic Testing Marketplace

by Dr. Hsien-Hsien Lei
Posted October 15, 2008 in DNA Testing, DNA and Disease

Fresh on the heels of the launch of the deCODE BreastCancer genetic test last week, Dr. Arthur Caplan, renowned director of the University of Pennsylvania Center for Bioethics, said in an article for MSNBC.com that breast cancer gene tests are not worth the price.

If you are worried about your risk of getting the disease, or are thinking about getting a genetic test done for any other reason, talk with your doctor or a genetic counselor who can determine whether your family history justifies the expense. You may be surprised to find that you can make changes in lifestyle and monitoring your own health that can reduce your risk without testing.

Dr. Caplan even goes so far as to accuse genetic testing companies of corporate greed which, given the current economic environment in the U.S., is bound to send shivers down their spine.

With respect to deCODE’s breast cancer genetic test, it examines seven single nucleotide polymorphisms* (SNPs) that are purportedly involved in 60 percent of all breast cancers. Results from the test are given as personal lifetime relatively risk compared to the general population (specifically people of European descent). Other risk factors such as family history, pregnancy history, etc. are not taken into consideration when calculating a deCODE BreastCancer genetic test taker’s risk.

deCODE’s Chief Scientific Officer, Dr. Jeff Gulcher, responded to Dr. Caplan on its blog, deCODE You (a member of the DNA Network) and drew analogies between the BreastCancer genetic test and LDL-cholesterol tests. Anyone who is identified to be at higher risk of breast cancer (or in the analogy, high cholesterol leading to cardiovascular disease) would benefit from greater vigilance, more intensive screening, and possibly, preventive therapy.

Another DNA Network member, Dr. Steve Murphy at Gene Sherpas calls the deCODE BreastCancer test “hype.” Cancer Research UK also believes that “it’s too early for a test of this kind to be released to the general public.” Dr. Len Lichtenfeld of the American Cancer Society does not believe the test will “advance our cause in the fight to reduce deaths from cancer in a meaningful, evidence-based and scientifically accurate way.”

Speaking of cost, though,it seems that 23andMe customers get the better deal because all of the six of the seven SNPs (rs4415084 was on the v1 chip but not on the v2 chip) examined in the deCODE BreastCancer genetic test are included on version 2 of the 23andMe gene chip (I checked using SNPedia) not to mention the other nearly 600,000 SNPs included in the 23andMe report. A 23andMe DNA test costs $399 while a deCODE BreastCancer genetic test costs $1,625.

deCODE’s test offers other bits and fancy algorithms for calculating risk to justify the price. But customers should be aware that there is more than one way to get the genetic data they desire. And that data’s worth can be hard to price.

*See the list of SNPs in this sample report (pdf).

via Al’s Morning Meeting at Poynter Online

NB: I am a consultant to DNA Direct, a genetic testing company.

Photo Credit: abbyladybug

*Thanks to Mike Cariaso of SNPedia for clarifying what’s on the 23andMe chips.

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Chromosome 20 Involved in Male Pattern Baldness

by Dr. Hsien-Hsien Lei
Posted October 13, 2008 in DNA Testing, DNA and Disease

Consumers of genetic testing can now get more information on male pattern baldness from chromosome 20. A genetic test specific for hair loss is already on the market - HairDX. It examines CAG repeats in the androgen receptor gene (AR) on the X chromosome. According to Technology Review, in one study of 2,000 balding men and women, 1 in 7 Caucasian men had markers on both chromosome 20 and the X chromosome that increased their risk of baldness.

Lest you think baldness is a purely cosmetic concern, there is a link between male pattern baldness and increased risk of cardiovascular disease and insulin resistance. In 2000, the Physicians’ Health Study found that “vertex pattern baldness is a marker for increased risk of coronary heart disease events, especially among men with hypertension or high cholesterol levels.”

Interestingly, the HairDX website makes no mention of the link between hair loss and heart disease. Perhaps because they don’t want to run into trouble for making any innuendos about the medical utility of their DNA test. However, with this bit of information in mind, I’m less likely to make jokes at their expense.

Photo credit: Helge Carlsen

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My Son, The Genetic Epidemiologist

by Dr. Hsien-Hsien Lei
Posted September 16, 2008 in DNA Fun, DNA and Disease

My six-year-old’s reading and mark-up (in purple) of a paper in Nature Genetics authored by my friend, Dr. Linda Kao.

Press Release - New gene variant identified for nondiabetic end stage renal disease in African-Americans

Scientists at Johns Hopkins schools of Public Health and Medicine have, for the first time, identified variants in the gene MYH9 that are associated with increased risk for non-diabetic end stage renal disease (ESRD,) which is the near-loss of kidney function leading to either dialysis of transplant. MYH9, located on the 22 chromosome, is the first gene identified for common forms of kidney disease. The study was published online September 14 in the journal Nature Genetics and will be published in the October print edition. In a separate study published in the same issue, researchers at the National Institutes of Health reported similar findings.

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Helix Health Genomic Medicine Webcast

by Dr. Hsien-Hsien Lei
Posted May 20, 2008 in DNA and Disease

Whoa! Almost missed it.

Fellow DNA Network member, Dr. Steven Murphy, and his company, Helix Health, will be hosting a webcast tomorrow, May 21, 2008 at 1:00 pm EDT.

How Genomic Medicine Is Changing the Management of Breast & Ovarian Cancer

Registration is free and will feature Jessica Queller, author of Pretty is What Changes: Impossible Choices, The Breast Cancer Gene and How I Defied My Destiny.

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23andMe Collaborates on Study of Parkinson’s Disease Genetics

by Dr. Hsien-Hsien Lei
Posted May 15, 2008 in DNA and Disease

Researchers are rarely study participants. Up until last week, I’d only had a hand in designing and conducting epidemiologic studies and no experience at all participating in one. While waiting for my prenatal check-up, a master’s degree student at Imperial College recruited me for her thesis study on stress and comorbidity in pregnant women. I was happy to help out since I know firsthand how hard recruiting can be especially since she told me she’d had to reduce her sample size from 200 to 100 because it was such tough going.

All I had to do was check the boxes on about 10 pages of questions and collect a total of six saliva samples over two days. Two samples are taken upon waking and another around 9 pm. I’m sorry to say that on the first day, I forgot that I was supposed to sit still while the cotton plug was under my tongue for two minutes absorbing saliva and I also forgot to take my night-time sample at 9 and did it at 10:30 instead. I was also supposed to mail my frozen samples in by regular mail this past Monday or Tuesday but got distracted so it will have to wait until next week.

What a lousy study participant I am especially given that I know what it’s like to be on the other side!

Perhaps 23andMe and the Parkinson’s Institute and Clinical Center will have more compliant study participants. They are planning a Web-based study of Parkinson’s disease that will ask 150 people to donate their saliva for genetic analysis like any 23andMe customer as well as submit personal data via the Web. In addition, the study will validate the online data collection method with face-to-face or phone interviews.

The San Francisco Chronicle reports that 23andMe also hopes that pharmaceutical companies will pay them for access to personal genomics customers who have specific conditions or disorders. Linda Avey is quoted as saying the pharmaceutical companies would be contacting customers to offer them the opportunity to participate in clinical trials (where 23andMe may also be able to offer database services) but I can easily see this extending into personalized ads for personalized medicine. Could be both good and bad.

From my recent and previous personal experiences, interviewer-led data collection will always be the gold standard because participants can ask for clarification on sample collection instructions and questions. However, being able to complete questionnaires in the comfort of one’s own home without time pressure (I was in a rush in case I was called in for my appointment), may increase the accuracy of the data being collected. The 23andMe Parkinson’s disease study will be valuable not only for its potential genetic discoveries, but also for its insights into the implementation of the Web in scientific research. Unfortunately, there’s no easy way for me to spit my sample into them series of Internets tubes so I guess I’ll still have to remember to schlep them to the mailbox on Monday.

Photo credit: David Wilmot on Flickr

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DNA Podcast: Genetic Testing and Adolescents

by Dr. Hsien-Hsien Lei
Posted April 5, 2008 in DNA Podcasts and Videos, DNA Testing, DNA and Disease

powered by ODEO

In this Melbourne University Up Close podcast, Dr. Shane Huntington interviews Dr. Rony Duncan of the Murdoch Children’s Research institute about genetic testing and adolescents. A full transcript is also available.

If we allow young people to have that information about their future, or if we allow parents to test their children and obtain that information, what happens if those children grow up and decide that they don’t want the information and decide that they didn’t actually make an informed choice?

Also see my previous post - American Journal of Medical Genetics Special Issue on Children and Genetics.

via ScienceAlert

(>> Start a discussion!)

SNPs on Chromosome 15 Associated with Smoking and Lung Cancer

by Dr. Hsien-Hsien Lei
Posted April 3, 2008 in DNA and Disease

Despite recent downsizing, deCODE Genetics has published a new study in Nature on the genetics of smoking and lung cancer. Two other studies with the same focus were also published in Nature and Nature Genetics.

All three studies identified regions on chromosome 15 that are associated with nicotine dependence, lung cancer, and peripheral artery disease. The deCODE study focused on SNP rs1051730 located on chromosome 15q24 in the CHRNA3 nicotine acetylcholine receptor. People with one copy of the “T” version of this SNP had:

• 30% increase in risk of lung cancer
• 20% increase in risk of peripheral artery disease

Half of people of European descent have at least one copy of the higher risk SNP and 10% may have two copies which increases their cancer risk by 80%.

• A smoker has a 15% risk of lung cancer over his/her lifetime
• Smokers with two copies of the T SNP variant has a 23% risk of lung cancer.
• People who’ve smoked less than 100 cigarettes in their lifetime have a <1% risk of lung cancer.

Researchers also hypothesized that the higher risk T SNP variant may influence a person to smoke more cigarettes and become more easily dependent on nicotine. The deCODE study found that those with one copy of the T SNP variant smoked an additional cigarette per day than those without the variant. Two copies of the T SNP variant was associated an two more cigarettes per day.

Last month for No Smoking Day in the UK, Alicia Sparks at Mental Health Notes gave five reasons why smoking is dangerous to her mental health. Aside from the obvious negative health effects, she says smoking does not make her happy, makes her worry, gives her too much to deal with, stresses her out, and makes her feel guilty. What do you think about smoking?

NB: Bioethicist Arthur Caplan discussed the possibility of lung cancer genetic testing in the New York Times.

Such testing could carry risks all its own, bioethicist Arthur Caplan of the University of Pennsylvania warned. People who have been found to have a genetic predisposition to addiction and lung cancer could find it harder to get health or life insurance, or their employer might drop their coverage, he said.

”The good news is that getting these risk estimates will help focus anti-smoking campaigns, and some people will want to voluntarily get into anti-addiction programs early, where they will probably work better,” Caplan said in an e-mail. But if such testing is done, it should be voluntary, and the results should be kept private, he said.

Update: Dr. Ann Turner comments on these findings at GENEALOGY-DNA.

The SNP, rs1051730, has already been incorporated into reports for deCODEme customers (literally within a few minutes of the press release). It is also tested by 23andMe, but it is not on the Affymetrix 6.0 chip used by SeqWright and a new company http://geneessence.com. However, the Affy chip could have a near-by SNP that would be in linkage disequilibrium with rs1051730.

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Genes May Increase Chance of Baby Born Breech

by Dr. Hsien-Hsien Lei
Posted March 31, 2008 in DNA and Disease

At my 30-week prenatal visit last week, the doctor told me the baby was in a transverse position. Hopefully she’ll get her little rear in gear at my 34-week visit and be head down unless she wants to be really ornery as only about 3 percent of babies are breech at birth (buttocks or the feet down). Her older brother was in the “correct” position almost the entire time so I can tell she’s going to be a handful!

Risk factors for breech delivery include:

• First baby
• Older mother
• Low gestational age
• Low birth weight
• Uterine malformations
• Pelvic tumours
• Site of placental attachment
• Low volume of amniotic fluid
• Congenital anomalies

Breech delivery is associated with increased perinatal mortality and morbidity.

One reason I’m not worrying too much is because a large population-based study in Norway was published last week in BMJ that showed breech deliveries are more common if the baby’s parents were born breech themselves. I know I was not born breech and I’ll assume my husband wasn’t either or my mother-in-law would have mentioned it. If the mother or father was born breech, their baby has an approximately 2-fold increase in odds of being born breech as well. The authors conclude:

Intergenerational recurrence risk of breech delivery in offspring was equally high when transmitted through fathers and mothers. It seems reasonable to attribute the observed pattern of familial predisposition to term breech delivery to genetic inheritance, predominantly through the fetus.

They also recommend that parents who were born breech inform their healthcare providers so their babies can be more closely monitored if necessary.

Please cross your fingers for me!

Image: Newborn baby from Wellcome Images under Creative Commons

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