Leading personal genomics company reviews last year's genetic milestones on the journey to understanding the role of genetics in personal health, human development and ancestry
MOUNTAIN VIEW, CA – January 11, 2011 – 23andMe has released its first annual list of what it felt to be the 10 most interesting and significant genetic findings in 2010, as part of an ongoing journey to understand the role of genetics in personal health and human development.
"Our understanding of the human genome is accelerating at a phenomenal rate," stated Anne Wojcicki, co-founder and CEO of 23andMe. "Below we have compiled a list of our top ten favorite genetic discoveries from 2010. We look forward to exploring more discoveries in 2011."
Customers of 23andMe have the opportunity to learn about how their genetics can influence their individual health traits, risk for developing certain diseases and conditions, reactions to a variety of medications, and ancestry. Throughout the year, 23andMe monitors scientific publications for studies that provide exciting glimpses into these areas. The company provides information on these developments to its customers through continual updates to their Health and Traits reports, as well as "SNPwatch" postings to the company's public blog, "The Spittoon."
While 23andMe provides updates on genetic research on a regular basis, it recognizes and cautions that in most cases more studies are needed before the research can provide information of specific value to individuals. 23andMe therefore states that the studies described in The Spittoon's SNPwatch series are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice and individuals should always seek the advice of their physician or other appropriate healthcare professional with any questions regarding diagnosis, cure, treatment or prevention of any medical condition.
1. Genetics influences whether your body shape is "apple" or "pear" — and which shape you are has implications for disease.
If you've been looking at an apple or pear body shape in the mirror, take a closer look at your genetic variants. This fall, 23andMe reported on new research connecting common genetic variants with propensity towards apple- and pear- body shapes. A large analysis by the Genetic Investigation of Anthropometric Traits (GIANT) consortium investigated how genetics influence waist and hip size in nearly 200,000 people from more than 50 studies. Published in Nature Genetics, the report identified 14 single nucleotide polymorphisms (SNPs, or common genetic variants) — 13 new and one previously reported — associated with body fat distribution. These findings have health implications because "apples", whose weight concentrates around their middles, appear to be at greater risk for developing heart disease and type 2 diabetes than their pear counterparts.
In addition to the exciting new genetic associations, results from this study suggest that genetics play a more significant role in determining body fat distribution in women than in men. As with obesity and many other conditions with a strong environmental component, genes only account for a small piece of the puzzle underlying variability in body fat distribution. Even so, this study made an interesting observation: the variants associated with body fat distribution (measured by waist-hip-ratio) in their study subjects appeared to be mostly distinct from those variants associated with overall body fat content (measured by body mass index (BMI)). Since the location of body fat plays an important role in disease risk, a better understanding of the genetic risk factors underlying increased waist and hip size may lead to improved therapies or lifestyle recommendations. 23andMe customers are able to view data for nine variants associated with apple versus pear body shape from this study.
"SNPwatch: Apple or Pear? How Genes Help Shape Your Shape," Oct 19, 2010. The Spittoon. http://spittoon.23andme.com/2010/10/19/snpwatch-apple-or-pear-how-genes-help-shape-your-shape/
Heid IM et al. (2010) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 42:949-960.
2. Genetic variations newly associated with risk for childhood asthma
New regions of the genome associated with childhood asthma, a growing public health concern throughout the US affecting more than seven million children, were found by researchers from the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP) and the GABRIEL consortium, as published in two studies in the New England Journal of Medicine. In the first study, analysis of DNA from about 1,700 children with asthma and 3,500 controls, all of European ancestry, identified several genetic variants on chromosome 1 associated with the risk of developing childhood asthma. Many of these same variants were then also found to be associated with risk for asthma in a sample of more than 1,600 African American children with asthma and 2,045 controls. All of the newly identified variants are located near the gene that encodes DENND1B, a protein known to be involved in the body's response to foreign particles.
The chromosome 1 variants identified by the CHOP researchers affected the odds of childhood asthma in different ways depending on ethnicity. Versions of the SNPs associated with increased risk in African Americans were associated with decreased risk in the European sample. This is not unusual in genetic studies, and often reflects differences in the genetic backgrounds of different populations.
In the second study, researchers identified associations between variants on chromosomes 2, 6, 9, 15, and 22 and asthma in individuals with European ancestry, with stronger effects for childhood asthma. They also observed that a previously reported association between a region on chromosome 17 and asthma was specific to childhood asthma only. When the researchers looked for genetic associations with allergy susceptibility (a condition that is often linked to asthma) they found very little overlap, suggesting that allergy sensitivity may be an effect of asthma rather than its cause.
The two studies' findings could lead eventually to the development of new types of treatments for childhood asthma. Previous research linking genetic variants on chromosome 17 with the risk for childhood asthma in Europeans suggested that these variants have an effect only in children who are exposed to tobacco smoke. More research will be needed to work out the details, but the importance of chromosome 17 in asthma was further supported by both of the current studies, which replicated the previous findings in addition to identifying new variants associated with the disease.
"SNPwatch: Breath Easier... New Insights From Asthma Research." Oct 26, 2010. The Spittoon. http://spittoon.23andme.com/2010/10/26/snpwatch-breathe-easier-new-insights-from-asthma-research/
"SNPwatch: More Progress in the Search for Genetic Variants Linked to Childhood Asthma." Jan 25, 2010. The Spittoon. http://spittoon.23andme.com/2010/01/25/snpwatch-more-progress-in-the-search-for-genetic-variants-linked-to-childhood-asthma/
Sleiman PA et al. (2010) Variants of DENND1B Associated with Asthma in Children. New Eng J Med. 362:36-44.
Moffatt MF et al. (2010) A Large-Scale, Consortium-Based Genomewide Association Study of Asthma. New Eng J Med. 363: 1211-1221.
Rheumatoid arthritis is a common autoimmune disease in which the individual's own immune system attacks the lining of the joints, causing stiffness and muscle aches. Like other autoimmune diseases, development of rheumatoid arthritis is likely caused by a complex combination of genetic and environmental factors. Recent research into the genetics of the disease has identified many of the genetic factors, and new studies continue to implicate additional variants that may influence risk.
This year, SNPwatch presented a pair of studies published in Nature Genetics which found several new genetic variants associated with rheumatoid arthritis. A research team in Japan at the RIKEN Center for Genomic Medicine identified a variant, rs3093024, associated with rheumatoid arthritis risk in Japanese individuals. The second study, from Brigham and Women's Hospital in Boston, confirmed the same association in individuals with European ancestry. In both studies, each copy of the A version of the variant increased an individual's odds of the disease by 1.1 to 1.2 times.
The RIKEN team demonstrated that the different versions of rs3093024, already connected to risk of Crohn's disease, affect the behavior of the CCR6 gene, providing a potential biological explanation for the variant's contribution to rheumatoid arthritis risk. The Brigham and Women's team also found several other genomic regions associated with rheumatoid arthritis in people with European ancestry, some of which had not yet been linked to autoimmune disease.
"SNPwatch: Two Studies Connect More Immune System Genes to Rheumatoid Arthritis." May 12, 2010. The Spittoon. http://spittoon.23andme.com/2010/05/12/snpwatch-two-studies-connect-more-immune-system-genes-to-rheumatoid-arthritis/
Kochi Y et al. (2010) A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 42:515-519.
Stahl EA et al. (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 42:508-514.
Alzheimer's disease is the most common cause of dementia in people 65 years and older, and will become an increasing health concern as the population of the United States (and many other nations) ages. Currently more than five million Americans are thought to have the disease, but by the year 2050 that number is estimated to reach 14 million unless a cure or prevention method is developed.
Until very recently, mutations in only one gene — APOE — had been conclusively associated with the more common late-onset form of Alzheimer's (there are other mutations associated with early-onset, familial Alzheimer's disease). In the last few years, however, research groups studying large numbers of people have identified variants in several new genes with small effects on the disease.
As 23andMe reported in SNPwatch, researchers pulled together the results of several studies to find new Alzheimer's associated risk variants. The scientists, whose results appear online in the Journal of the American Medical Association, suggest that these variants may be important for unraveling the underlying biology of Alzheimer's, which will be essential in the quest to find new methods of treatment. The combined analysis also provided support for previously identified associations in the CLU and PICALM genes, but failed to confirm a third previously reported association in the CR1 gene with Alzheimer's disease.
Researchers from the CHARGE, GERAD1 and EADI1 Alzheimer's research consortia combined data from tens of thousands of people with European ancestry. The results of their analysis implicated SNPs rs744373 near the BIN1 gene and rs597668 near theEXOC3L2/BLOC1S3/ MARK4 genes. The BIN1 gene encodes a protein that is highly expressed in the brain and known to be important in processes that are disrupted by the plaques that form in the brains of people with Alzheimer's. Two of the genes near rs597668, BLOC1S3 and MARK4, encode brain proteins that are also involved in processes that are disrupted in Alzheimer's disease. The MARK4 protein in particular is interesting because it interacts with tau, the protein responsible for the tangles seen in the brains of people with Alzheimer's.
Although risk models that incorporated an individual's information for the two replicated CLU and PICALM gene regions did not substantially improve prediction compared to a traditional model using only APOE status, age and sex, Nancy Pedersen of the Karolinska Institute in Sweden, points out in an accompanying editorial that this finding is not surprising given the small effect of these SNPs on risk and "only verifies the notion that AD is a polygenic disorder; i.e., that potentially tens of thousands of risk alleles, each with a small effect, are important for liability to disease. What is remarkable is that the single gene APOE is as important as it is for this complex disorder, and that right now, the most important thing doctors can do is encourage people to make lifestyle changes, especially those that improve cardiovascular health, that may reduce the risk of dementia or at least postpone it."
"SNPwatch: Large Study Identifies Two More Genetic Variants Associated with Alzheimer's Disease." May 11, 2010. The Spittoon. http://spittoon.23andme.com/2010/05/11/snpwatch-large-study-identifies-two-more-genetic-variants-associated-with-alzheimers-disease/
"SNPwatch: Largest Alzheimer's Genetic Studies To Date Identify Three New Susceptibility Genes." Sep 8, 2009. The Spittoon. http://spittoon.23andme.com/2009/09/08/snpwatch-largest-alzheimers-genetic-studies-to-date-identify-three-new-susceptibility-genes/
Seshadri S et al. (2010) Genome-wide Analysis of Genetic Loci Associated with Alzheimer Disease. J Am Med Assoc. 303(18):1832-1840.
Pedersen NL. (2010) Reaching the Limits of Genome-wide Significance in Alzheimer Disease. J Am Med Assoc. 303(18):1864-1865.
Harold D et al. (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 41:1088-1093.
Lambert J et al. (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet. 41:1094-1099
The old adage, "take two aspirin and call me in the morning," doesn't work as well as we might think. It turns out that one size doesn't fit all when it comes to drug response, and for some people, certain drugs might be more effective, not work at all, or even produce serious side effects. The growing body of pharmacogenomics research has helped us understand that, at least in part, genetics play a role in how well some drugs work for different people. The 23andMe Drug Response reports link customers' genetics to the way they might respond to certain drugs and medications. The results range from whether you're likely to benefit from a drug, need a different dose due to sensitivity, experience toxic or adverse effects, or even have increased risk for other conditions. 23andMe cautions that its Drug Response reports should not be used to independently establish, abolish, or adjust medical treatment and medications but should be discussed with your physician. Only a medical professional can determine whether a particular drug or dose is appropriate for you.
In addition to connecting customers' genetics to the latest research in pharmacogenomics, 23andMe is actively researching the genetic basis underlying differences in individuals' responses to drugs. As the year drew to a close, 23andMe announced that, with funding from the National Institutes of Health, it is launching a multi-part pharmacogenomic research project. The first phase of the project will attempt to replicate known genetic effects that influence the efficacy and tolerability of three classes of medications: Warfarin, a commonly prescribed blood thinner; proton pump inhibitors, the most frequently prescribed medications for acid reflux; and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen.
In 2007 and again in 2010, the FDA updated the labeling for warfarin to include information about how variations in two genes, CYP2C9 and VKORC1, can impact a patient's optimal dose of the drug. The latest update provided initial dosage recommendations for patients with different variant combinations. Studies are ongoing to determine the cost-benefits of using genetic testing to improve drug dosing; the results of such studies will influence whether and how quickly personal genetic information becomes a routine part of medical care. In August, The Spittoon covered these developments with an in-depth perspective of the complicated history and potential future of pharmacogenomics.
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