A paper published in the New England Journal of Medicine (NEJM) this week, entitled “Performance of Common Genetic Variants in Breast-Cancer Risk Models,” has led several media outlets to declare that common genetic variants have nothing to add when it comes to predicting breast cancer risk.  Here we’ll explain how the results of this study have been misinterpreted.

Researchers from the National Cancer Institute and other institutions looked at data from 5,590 women with breast cancer and 5,998 women without the disease.  These women, all between 50 and 79 years old, had participated in one of five studies, four in the United States and one in Poland.  Since it’s known already which women have or have had breast cancer, and which have not, the researchers were able to use their data, both genetic and non-genetic, to test the predictive power of different types of risk calculations.

The study tested five different models.  The “demographic model” considered only age, year of entry into the study and which study the woman was originally part of.  The “nongenetic model” added in several variables that are part of the so-called “Gail model,” which is the standard model used in clinical practice today to counsel women about their risk.  These variables were the number of first-degree relatives with a diagnosis of breast cancer, age at menarche, age at first live birth, and number of previous breast biopsies.  Two models used the demographic information plus genetic information for 10 SNPs (they differed in details of how the genetic risk score was calculated).  Finally, the “inclusive model” combined demographics, the Gail model and the genetic information.

The genetic models and the nongenetic model performed about the same, with genetics doing just a little bit better.  Perhaps not surprisingly, the best model was the one that used the most information.  With the inclusive model, which is based on genetic and non-genetic information, there was a net 12% improvement in risk classification over the nongenetic model for women with breast cancer. Continue Reading »

Tags: breast cancer, National Cancer Institute, NEJM, New England Journal of Medicine, risk, SNPs

Spring is about to, well, spring.  And for many of us, that means breaking out the Benadryl® and the tissues as pollen fills the air and our allergies kick in.

Allergies are part of the daily lives for one out of four Americans, making allergies more common than heart disease, cancer and diabetes combined.  For many people, allergies involve only symptoms that are a nuisance, like sneezing or itchy eyes.  But for some, contact with certain substances can lead to life-threatening anaphylactic shock.  To study this mysterious and growing problem, we’ve released our first allergy survey.

Allergies occur when your body reacts to a normally harmless substance, called an allergen, like it’s a dangerous invader.  Your immune system produces IgE antibodies that recognize the allergen and trigger the release of histamines.  While histamines normally help protect your body against infections, they can cause allergy symptoms when released inappropriately.  This is why many allergy medications are called “anti-histamines”. Continue Reading »

Tags: allergy, histamines, hygiene hypothesis, pollen, spring, survey

Today the National Institutes of Health (NIH) announced its plans to create a public database in which genetic test providers will voluntarily deposit information about their services that can then be searched by researchers, consumers, health care providers, and others. The aim of this Genetic Testing Registry, which is expected to be launched in early 2011, is to enhance access to information about the availability, validity, and usefulness of genetic tests.

“The need for this database reflects how far we have come in the last 10 years,” said NIH Director Francis S. Collins, M.D., Ph.D., in a press release. “The registry will help consumers and health care providers determine the best options for genetic testing, which is becoming more and more common and accessible.”

“We welcome the news of the Genetic Testing Registry,” said 23andMe co-founder Anne Wojcicki in response to the announcement.  “23andMe has always been committed to providing individuals with the information they need to make the most of their own genetic information.  We look forward to working with the NIH on this project.”

More information about the Genetic Testing Registry is available from the National Center for Biotechnology Information here.  Comments and questions can be submitted from this page.  There is also a list of background reading materials.

Francis Collins has done several interviews in the past few weeks where he has discussed the role of genetics in health care, now and in the future. A quick video interview with the Washington Post can be seen here.  An hour long interview he did on the Diane Rehm show is available here.

Tags: Anne Wojcicki, Francis Collins, Genetic Testing Registry, NIH

Today at the American College of Cardiology conference in Atlanta, researchers from the Mayo Clinic and Medco Health Solutions, Inc., presented results showing that using genetic testing to guide dosing of the commonly used blood thinner warfarin reduces hospitalizations.

Overall there were 31% fewer hospitalizations within six months of beginning warfarin therapy in those who received genetic testing compared to those who didn’t. A 28% drop in hospitalizations due specifically to bleeding or blood clots was seen.

“Warfarin represents an excellent example of how to take the modern science of genetic testing and apply it to making an older drug more effective and safer to use,” said Dr. Robert S. Epstein, lead author of the study and Medco’s chief medical officer and president of the Medco Research Institute, in a press release.  ”These results show that we can greatly reduce hospitalizations, and their significant costs, by making genetic testing routine early in a patient’s therapy with warfarin.” Continue Reading »

The U.S. Food and Drug Administration (FDA) has updated the label information for the commonly used anti-clotting medication Plavix® (clopidogrel) to stress to physicians that patients carrying certain genetic variations may not receive the full benefit from the drug.

Plavix reduces the chance a harmful clot will develop by preventing blood cells called platelets from sticking together. Usually prescribed in combination with aspirin, Plavix has been shown to help reduce the risk of subsequent heart attacks or strokes in people who have already suffered from a cardiovascular event. Plavix also reduces the risk of heart attack and stroke in people diagnosed with peripheral artery disease.  The drug is also is used to lower the risk of blood clots in people with unstable angina (chest pain) caused by partially blocked arteries and in those who have had a stent implanted to help keep their arteries open.

Once inside the body, Plavix is absorbed in the intestines and then converted into its active form by enzymes in the liver. But some people have genetic variations that reduce the activity of one of the most critical enzymes — CYP2C19. This, in turn, reduces the amount of active drug in the bloodstream and its effectiveness in preventing clots. Continue Reading »

Tags: black box, boxed warning, clopidogrel, CYP2C19, Effient, FDA, metabolizer, Plavix, prasugrel

Colorectal cancer is the third most common cancer (excluding skin cancers) and the second leading cause of cancer-related deaths in the United States. Each year about 150,000 people are diagnosed with the disease.

Risk factors for colorectal cancer include age (most cases occur in people over 50), ethnicity (African Americans and Ashkenazi Jews have particularly high rates of the disease), a personal history of colon polyps or colorectal cancer, and the presence of inflammatory bowel disease (Crohn’s disease or ulcerative colitis).  Obesity, physical inactivity, smoking and heavy drinking have also all been associated with increased risk for colorectal cancer.

Genetics contribute to a person’s colorectal cancer risk, although non-genetic factors seem to play a larger role.  About 5% of people with colorectal cancer, however, develop the disease as a result of either familial adenomatous polyposis (FAP) or Lynch syndrome, two cancer syndromes caused by serious genetic mutations.

Anyone with a family history of colorectal cancer should talk to their health care professional about what screening procedures, and possibly what genetic tests, are right for them.

Research to find common genetic variants associated with colorectal cancer risk has yielded several good associations, but together they explain only a small part of the genetic contribution to the disease. There are probably many more variants with small effects left to be found, as well as rare variants with larger effects.  23andMe customers can see their results for three replicated SNP associations in the Colorectal Cancer Research Report.  Spittoon posts addressing colorectal cancer can be found here, here, here and here. Continue Reading »

Tags: colorectal cancer, FAP, HNPCC, Lynch syndrome

Researchers have identified several genetic variations associated with the timing of a baby’s first tooth and the number of teeth at age one. The results, published recently in the journal PLoS Genetics, could be important for understanding more about human health than just this rite of passage all babies must go through.

Nascent teeth form in the womb, but for most babies the first one doesn’t poke through the gums until sometime between four and seven months of age. Some little ones, however, begin teething as early as three months, while others may take a year or more to sprout their first pearly whites. Although the genetic bases for many syndromes involving serious problems with tooth formation have been discovered, until now not much work has been done to understand how our DNA impacts the normal variation in teething seen in the population.

British and Finnish researchers analyzed the DNA of about 6,000 people (approximately 1,500 from the U.K. and 4,500 from Finland) who had been followed by epidemiologists since early in their mothers’ pregnancies. Genetic variants in 10 different regions of the genome had at least a suggestive link to age at first tooth eruption and/or number of teeth at one year. Those SNPs with statistically significant associations with at least one of the traits are shown in the table below. Continue Reading »

Tags: baby, development, PLOS Genetics, teeth

Faces of America is a four-part series in which Harvard scholar Henry Louis Gates, Jr. uses genealogy and genetics to explore the family histories of 12 renowned Americans in an effort to understand what made the United States the place it is today.

The final episode, “Know Thyself” airs this Wednesday (March 3) on PBS.  In this segment, DNA is used when the genealogical paper trails ends to give the participants an even deeper understanding of who they are and where they came from.

All of the participants who chose to learn about their genetics were analyzed using the 23andMe Ancestry Edition.  Our scientists Joanna Mountain and Brenna Henn (who make some cameo appearances!) helped with the analysis of the participants’ mitochondrial and Y chromosome haplogroups, global origins and ancestry paintings.

In addition to learning about their ancestors, Faces of America guests who choose to participate in our new Relative Finder feature will join the thousands of other people who now have the ability to find living relatives based on their DNA.

If you haven’t been watching this series, there’s still time to catch up on what well-known Americans Elizabeth Alexander, Mario Batali, Stephen Colbert, Louise Erdrich, Malcolm Gladwell, Eva Longoria, Yo-Yo Ma, Mike Nichols, Her Majesty Queen Noor, Dr. Mehmet Oz, Meryl Streep and Kristi Yamaguchi have learned about their family histories.  The first three episodes are all available online:

Episode 1: Our American Stories

Episode 2: Becoming American

Episode 3: Making America

Check your local listings for Faces of America here.

Tags: Dr. Mehmet Oz, Elizabeth Alexander, Eva Longoria, Faces of America, Henry Louis Gates Jr., Her Majesty Queen Noor, Kristi Yamaguchi, Louise Erdrich, Malcolm Gladwell, Mario Batali, Meryl Streep, Mike Nichols, PBS, Stephen Colbert, Yo-Yo Ma

Atrial fibrillation (AF) is the most common irregular heart rhythm, affecting one in four people over the age of 40. While not usually life-threatening on its own, individuals with the condition are at increased risk of stroke and heart failure. AF appears most frequently in older, male individuals with a history of obesity or cardiovascular problems, but some people develop it at a young age and with no obvious heart disease. This type of AF, known as “lone” AF, tends to run in families but is otherwise difficult to diagnose.

Previous studies covered by The Spittoon have linked common genetic variants to AF, but these studies have focused mainly on the typical, later-onset type of AF. Led by Patrick Ellinor and Stefan Kaab, a group of researchers from the United States and Europe investigated the genetic basis for lone AF in a group of about 1,300 people of European ancestry with the condition and more than 12,000 people without AF. Their study, published this week in Nature Genetics, connected the genetic variant rs13376333 with increased risk of lone AF.

In their analysis, each copy of the T version of rs13376333 increased the odds of lone AF by 1.52 times compared to two copies of the C version. The T version was also associated with an increased risk of typical AF, but the effect was smaller – only 1.13 times higher odds of having the condition for each copy.

(23andMe Complete Edition customers can check their data for rs13376333 using the Browse Raw Data feature.)

The variant is located near KCNN3, a gene that codes for an ion channel responsible for controlling the movement of potassium in and out of cells. KCNN3 ion channels in particular are found in “excitable” tissues such as the brain and heart. In mice, abnormalities in the behavior of the KCNN3 gene have been associated with increased blood pressure, but the exact role of KCNN3 in the human heart is unclear. Further research is needed to explore whether KCNN3 may have therapeutic applications for treatment of AF.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Tags: atrial fibrillation

The journal Current Biology has a special review issue on the global genetic history of Homo sapiens.  The articles are written for a fairly technical audience, but if it’s a topic you’re interested in, you might want to check it out.  All of the articles are available online for free.

• Archaeogenetics — Towards a ‘New Synthesis’?
• The Evolution of Human Genetic and Phenotypic Variation in Africa
• The Archaeogenetics of Europe
• The Human Genetic History of South Asia
• The Human Genetic History of East Asia: Weaving a Complex Tapestry
• The Human Genetic History of Oceania: Near and Remote Views of Dispersal
• The Human Genetic History of the Americas: The Final Frontier
• The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation

Tags: archaeogenetics, Current Biology, evolution, human genetic history