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Public release date: 26-Oct-2011[ | E-mail |
Share ] Contact: John Rodgers
jdr2001@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Research may lead to highly targeted, individualized therapies
NEW YORK -- In what is so far the largest investigation of its kind, researchers uncovered a wide range of new insights about common diseases and how they are affected by differences between two persons' genes. The results from this study could lead to highly targeted, individualized therapies.
Led by researchers from Weill Cornell Medical College in Qatar and published in a recent edition of the journal Nature, the study provides details on the genetics behind many diseases, including cardiovascular and kidney disorders, diabetes, cancer, gout, thrombosis and Crohn's disease, and elucidates the role that individual differences in metabolism play in these disorders.
Disturbances in metabolism are at the root of a variety of human afflictions and complex diseases. Although many of the genes that contribute to these conditions have been identified since the completion of the Human Genome Project in 2003, it is still not known how metabolic disorders related to these genetic aberrations disrupt cellular processes.
One hundred years ago, Archibald Garrod, one of the fathers of modern biochemistry, realized that inborn errors in human metabolism are "merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees" and that this "chemical individuality [confers] predisposition to and immunities from the various mishaps which are spoken of as diseases." Ever since, identification of the genetic basis of human chemical individuality has been elusive.
Now researchers addressed this challenge by using a new technology, called metabolomics. They measured the levels of more than 250 biochemical compounds in over 60 metabolic pathways, including lipids, sugars, vitamins, amino acids and others in blood from over 2,800 individuals. They then combined this dataset with information on more than 600,000 genetic variants (SNPs) that were detected in the genes of each of the study participants. Most of the SNPs were located in genes known to encode proteins involved in the relevant metabolic pathways. Fifteen of the SNPs had previously been associated with metabolism-related conditions, such as cardiovascular disease, kidney disease, gout, diabetes, gastrointestinal diseases, cancer and adverse drug reactions. But the new findings also uncovered a wealth of new associations that link the genetic makeup of a person to his or her biochemical capacities. This data is publicly available in an online database, accessible at http://www.gwas.eu.
Given the exceptional size of the dataset, the researchers prioritized the data to focus on 37 SNPs that were most strongly associated with metabolic traits, 23 of which had never been described before. The 37 SNPs had very large effects on the individuals' metabolite levels and can be considered to constitute what the authors call the "genetic basis of human metabolic individuality."
First author Dr. Karsten Suhre, professor of physiology and biophysics and director of the Bioinformatics Core at Weill Cornell Medical CollegeQatar, says, "These findings will enable researchers to identify new and potentially relevant metabolic processes and pathways. Two highly sophisticated biochemical measurement methods -- genetics and metabolomics -- applied to only two drops of blood can reveal deep insights into the genetic make up of our metabolic capacities. In addition to providing functional insights into the genetic basis of metabolic traits and complex diseases, this information is a way to understand an individual's uniqueness so as to develop highly targeted, personalized therapies and enable novel types of treatments or prevent adverse drug reactions."
###
In addition to Dr. Suhre, study co-authors include So-Youn Shin, Panos Deloukas and Nicole Soranzo of Wellcome Trust Sanger Institute; Ann-Kristin Petersen, Elisabeth Altmaier, Gabi Kastenmller, Christian Gieger, Christa Meisinger, Cornelia Prehn, Janina S. Ried, Werner Rmisch-Margl and Thomas Illig of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health; Robert P. Mohney and Michael V. Milburn of Metabolon Inc.; David Meredith of Oxford Brookes University; Brigitte Wgele, Martin Hrab de Angelis, Thomas Meitinger, Hans-Werner Mewes and Jerzy Adamski of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health and Technische Universitt Mnchen; Jeanette Erdmann of Medizinische Klinik II; Elin Grundberg of Wellcome Trust Sanger Institute and King's College London; Christopher J. Hammond, Massimo Mangino, Kerrin S. Small, Guangju Zhai and Tim D. Spector of King's College London; Anna Kttgen of University Hospital Freiburg; Florian Kronenberg of Innsbruck Medical University; Johannes Raffler of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, and Ludwig-Maximilians-Universitt; Nilesh J. Samani of University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital; H.-Erich Wichmann of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, Ludwig-Maximilians-Universitt, and Klinikum Grosshadern; and CARDIoGRAM.
Weill Cornell Medical CollegeQatar
Weill Cornell Medical College in Qatar is part of Weill Cornell Medical College. It was established in 2001 through a partnership between Cornell University and Qatar Foundation. WCMC-Q offers an innovative educational program that includes a two-year premedical program followed by a four-year medical program leading to the M.D. degree from Cornell University. Each program has a separate admission process guided by the standards of admission at Cornell University in Ithaca and its Medical College in New York City. For more information, visit http://www.qatar-weill.cornell.edu.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit http://www.weill.cornell.edu.
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Public release date: 26-Oct-2011[ | E-mail |
Share ] Contact: John Rodgers
jdr2001@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Research may lead to highly targeted, individualized therapies
NEW YORK -- In what is so far the largest investigation of its kind, researchers uncovered a wide range of new insights about common diseases and how they are affected by differences between two persons' genes. The results from this study could lead to highly targeted, individualized therapies.
Led by researchers from Weill Cornell Medical College in Qatar and published in a recent edition of the journal Nature, the study provides details on the genetics behind many diseases, including cardiovascular and kidney disorders, diabetes, cancer, gout, thrombosis and Crohn's disease, and elucidates the role that individual differences in metabolism play in these disorders.
Disturbances in metabolism are at the root of a variety of human afflictions and complex diseases. Although many of the genes that contribute to these conditions have been identified since the completion of the Human Genome Project in 2003, it is still not known how metabolic disorders related to these genetic aberrations disrupt cellular processes.
One hundred years ago, Archibald Garrod, one of the fathers of modern biochemistry, realized that inborn errors in human metabolism are "merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees" and that this "chemical individuality [confers] predisposition to and immunities from the various mishaps which are spoken of as diseases." Ever since, identification of the genetic basis of human chemical individuality has been elusive.
Now researchers addressed this challenge by using a new technology, called metabolomics. They measured the levels of more than 250 biochemical compounds in over 60 metabolic pathways, including lipids, sugars, vitamins, amino acids and others in blood from over 2,800 individuals. They then combined this dataset with information on more than 600,000 genetic variants (SNPs) that were detected in the genes of each of the study participants. Most of the SNPs were located in genes known to encode proteins involved in the relevant metabolic pathways. Fifteen of the SNPs had previously been associated with metabolism-related conditions, such as cardiovascular disease, kidney disease, gout, diabetes, gastrointestinal diseases, cancer and adverse drug reactions. But the new findings also uncovered a wealth of new associations that link the genetic makeup of a person to his or her biochemical capacities. This data is publicly available in an online database, accessible at http://www.gwas.eu.
Given the exceptional size of the dataset, the researchers prioritized the data to focus on 37 SNPs that were most strongly associated with metabolic traits, 23 of which had never been described before. The 37 SNPs had very large effects on the individuals' metabolite levels and can be considered to constitute what the authors call the "genetic basis of human metabolic individuality."
First author Dr. Karsten Suhre, professor of physiology and biophysics and director of the Bioinformatics Core at Weill Cornell Medical CollegeQatar, says, "These findings will enable researchers to identify new and potentially relevant metabolic processes and pathways. Two highly sophisticated biochemical measurement methods -- genetics and metabolomics -- applied to only two drops of blood can reveal deep insights into the genetic make up of our metabolic capacities. In addition to providing functional insights into the genetic basis of metabolic traits and complex diseases, this information is a way to understand an individual's uniqueness so as to develop highly targeted, personalized therapies and enable novel types of treatments or prevent adverse drug reactions."
###
In addition to Dr. Suhre, study co-authors include So-Youn Shin, Panos Deloukas and Nicole Soranzo of Wellcome Trust Sanger Institute; Ann-Kristin Petersen, Elisabeth Altmaier, Gabi Kastenmller, Christian Gieger, Christa Meisinger, Cornelia Prehn, Janina S. Ried, Werner Rmisch-Margl and Thomas Illig of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health; Robert P. Mohney and Michael V. Milburn of Metabolon Inc.; David Meredith of Oxford Brookes University; Brigitte Wgele, Martin Hrab de Angelis, Thomas Meitinger, Hans-Werner Mewes and Jerzy Adamski of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health and Technische Universitt Mnchen; Jeanette Erdmann of Medizinische Klinik II; Elin Grundberg of Wellcome Trust Sanger Institute and King's College London; Christopher J. Hammond, Massimo Mangino, Kerrin S. Small, Guangju Zhai and Tim D. Spector of King's College London; Anna Kttgen of University Hospital Freiburg; Florian Kronenberg of Innsbruck Medical University; Johannes Raffler of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, and Ludwig-Maximilians-Universitt; Nilesh J. Samani of University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital; H.-Erich Wichmann of Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, Ludwig-Maximilians-Universitt, and Klinikum Grosshadern; and CARDIoGRAM.
Weill Cornell Medical CollegeQatar
Weill Cornell Medical College in Qatar is part of Weill Cornell Medical College. It was established in 2001 through a partnership between Cornell University and Qatar Foundation. WCMC-Q offers an innovative educational program that includes a two-year premedical program followed by a four-year medical program leading to the M.D. degree from Cornell University. Each program has a separate admission process guided by the standards of admission at Cornell University in Ithaca and its Medical College in New York City. For more information, visit http://www.qatar-weill.cornell.edu.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit http://www.weill.cornell.edu.
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2011-10/nyph-sig102611.php
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