Featured Research

from universities, journals, and other organizations

Genome-wide Association Scan For Genetic Determinants Of Warfarin Dose

Date:
November 20, 2008
Source:
American Society of Human Genetics
Summary:
A growing number of geneticists are using genome-wide association studies (GWAS) to systematically search for and identify single nucleotide polymorphisms (SNPs), which are single base changes in the human DNA sequence that can cause differences in genetic characteristics. GWAS may also detect genes that are associated with a particular health condition, or with variation in patient response to prescribed drugs.

A growing number of geneticists are using genome-wide association studies (GWAS) to systematically search for and identify single nucleotide polymorphisms (SNPs), which are single base changes in the human DNA sequence that can cause differences in genetic characteristics. GWAS may also detect genes that are associated with a particular health condition, or with variation in patient response to prescribed drugs.

In this session, Ralph E. McGinnis, Ph.D., a Statistical Geneticist at the Wellcome Trust Sanger Institute (Cambridge, UK), will discuss the results of new research that that he and his colleagues have recently completed which extends this genome-wide association scan (GWAS) method to investigate the genetic aspects of drug response (pharmacogenetics) related to predicting appropriate warfarin dose.

Warfarin is the most widely prescribed drug used to reduce blood clotting in order to protect high-risk patients from experiencing a stroke, deep vein thrombosis, pulmonary embolism, heart attack, or other serious coronary malfunction. However, a combination of genetic and non-genetic factors can cause patients to exhibit 10- to 20-fold variation in the required dose (RD) of warfarin needed to achieve an adequate level of blood thinning, which means that initial prescribed doses may be too low (risking blood clots and/or failure to protect the patient from developing life-threatening health conditions, such as stroke or heart attack) or too high (risking over-anticoagulation and severe bleeding). Therefore, associated SNPs and genes that are related to dose variation requirements could be used to better estimate the proper warfarin dose based on a patient's genetic makeup, thereby reducing the risk of adverse events caused by inappropriate dosing.

McGinnis' research team were among the first to show that a polymorphism in the warfarin drug target VKORC1 accounts for a major portion (~30%) of the variance in RD, and they have recently evaluated 1,523 Swedish patients from the Warfarin Genetics (WARG) cohort in the largest study to date showing likely patient benefit from genetic forecasting of RD. In this study, the researchers found that the strongest signals were clustered around VKORC1 (the gene of the warfarin drug target), and the second strongest signals were located at SNPs clustering in the warfarin-metabolizing gene CYP2C9.

Mc Ginnis and colleagues conducted additional analyses that tested each GWAS SNP's influence on warfarin dose after adjusting for the influence of already known genetic (VKORC1, CYP2C9) and non-genetic (age, gender, etc.) factors. These analyses identified another statistical signal with genome-wide significance that corresponded to a SNP that changes the protein coding sequence of the CYP4F2 gene. This finding was confirmed in a study of 588 additional Swedish patients.

In summary, the current research results suggest that the proportion of dose variation explained by known genetic factors is approximately 29% (VKORC1), 11% (CYP2C9) and 1.5% (CYP4F2). Furthermore, by also taking into account the around 15% contribution of non-genetic factors such as age and gender, researchers can predict at least 50% of warfarin dose variation, making pre-treatment dose forecasting for individual patients a realistic possibility.

Ralph E. McGinnis, Ph.D., is a Statistical Geneticist at the Wellcome Trust Sanger Institute (Cambridge, UK) whose research focus is identifying genes and DNA variants that cause complex genetic disease or alter response to therapeutic drugs (pharmacogenetics). He has recently analyzed data for genome-wide or large-scale association studies of celiac disease, coronary artery disease, type 1 diabetes, and response to warfarin.

This research was presented at the 58th Annual Meeting of The American Society of Human Genetics (ASHG) in Philadelphia, Pennsylvania on November 11-15, 2008.


Story Source:

The above story is based on materials provided by American Society of Human Genetics. Note: Materials may be edited for content and length.


Cite This Page:

American Society of Human Genetics. "Genome-wide Association Scan For Genetic Determinants Of Warfarin Dose." ScienceDaily. ScienceDaily, 20 November 2008. <www.sciencedaily.com/releases/2008/11/081116161738.htm>.
American Society of Human Genetics. (2008, November 20). Genome-wide Association Scan For Genetic Determinants Of Warfarin Dose. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2008/11/081116161738.htm
American Society of Human Genetics. "Genome-wide Association Scan For Genetic Determinants Of Warfarin Dose." ScienceDaily. www.sciencedaily.com/releases/2008/11/081116161738.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins