【medical-news】基因组图谱研究发现最大一组与心脏病首要风险因素相关的基因 - ...

 Genomic Mapping Study Finds Largest Set of Genes Related to Major Risk Factor for Heart Disease

ScienceDaily (Aug. 5, 2010) — Scanning the genomes of more than 100,000 people from all over the world, scientists report the largest set of genes discovered underlying high cholesterol and high triglycerides -- the major risk factors for coronary heart disease, the nation's number one killer. Taken together, the gene variants explain between a quarter and a third of the inherited portions of cholesterol and triglyceride measured in the blood.


Human heart illustration. (Credit: iStockphoto/Sebastian Kaulitzki)

The research, representing scientists from 17 countries, appears in two papers in the Aug. 5 issue of Nature.

The National Institutes Of Health's National Heart, Lung, and Blood Institute (NHLBI) is the lead funder of the research, with additional support from the National Human Genome Research Institute (NHGRI), the National Institute on Aging (NIA), and several other NIH components.

Genome-wide association studies, or GWAS, analyze DNA across populations to pinpoint hard-to-find genetic hotspots for common diseases that are thought to have many causes, both genetic and environmental. Previous gene-scanning approaches have turned up hints about the nature of inherited heart disease risk. The new results take science well beyond what was previously known, and pinpoint research directions to elucidate the molecular and cellular mechanisms by which genetic variants contribute to disease.

"Genetic studies that survey a wide variety of human populations are a powerful tool for identifying hereditary factors in health and disease," said study co-author and NIH Director Francis S. Collins, M.D., Ph.D. "These results help refine our course for preventing and treating heart disease, a health problem that affects millions of Americans and many more people worldwide."

The research team found 95 genetic variants -- arrangements of the nucleic acids in DNA that differ among people -- which contribute to changes in blood cholesterol and triglyceride levels in women and men of many ethnic backgrounds. Abnormal levels of blood cholesterol and of triglycerides are powerful risk factors for heart disease. Because high blood cholesterol on its own does not cause symptoms, doctors routinely do blood tests to assess individual risk, but they do not know how much risk of developing cardiovascular disease is inherited.

Of the genetic variants, 59 had not been known and thus provide new clues for developing effective medicines to combat heart disease.

A significant insight from this research is that many of the variants show up in the DNA of people of widely diverse backgrounds. That is because the scientists scoured the DNA from people participating in large, population-based heart disease studies, reflecting people of European, Eastern and Southern Asian, and African-American descent.

Together, research participants from NHLBI study populations contributed about half of the 100,000 genomes scanned. Among the NIH population-based studies involved in the research were the Framingham Heart Study; the Atherosclerosis Risk in Communities Study; the Cardiovascular Health Study; the SardiNIA Study; the Ages, Gene, Environment Study; the InCHIANTI Study; the Family Heart Study; the NHLBI Candidate Gene Association Resource Program; the NIH Pharmacogenetics Research Network; the deCODE MI Study; and the Women's Genome Health Study.

"The NHLBI is a leader in supporting long-term studies, including the decades-long Framingham Heart Study, that carefully track the health outcomes of large groups of people and generations of families." said NHLBI Acting Director Susan B. Shurin, M.D. "This genome-wide association study successfully demonstrates how cutting-edge genomics research can be leveraged by our past and current research investment in population-based studies assessing long-term health and disease."

The research team's other study probed deeply into one of the genetic variants identified in the accompanying GWAS analysis.

In the group's second study, the scientists had an unusual opportunity to follow up on the findings of the GWAS to determining how one unusual gene variant trips up cholesterol and triglyceride metabolism in mice. Previous studies had identified the same genetic variant in humans who were prone to deadly heart attacks: The variant is common in people of African American, Hispanic, Asian Indian, and Chinese ancestries. Having a genetically identical mouse model enables researchers to look further into the contribution of a particular genetic variant to inherited heart disease risk.

"The new findings point us to specific genetic signposts that allow us to understand more fully why many people from all walks of life have abnormal levels of cholesterol and other blood lipids that lead to heart disease," said Christopher J. O'Donnell, M.D., associate director of the Framingham Heart Study and senior advisor for genomics to the NHLBI acting director. "What's really exciting about this work is that we are moving from discovery to understanding brand-new information about how genes alter the lipids that contribute to heart disease."

In addition to the NHLBI, the NIA and the NHGRI, other NIH funding sources include the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Research Resources.

http://www.sciencedaily.com/releases/2010/08/100804133348.htm

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Genomic Mapping Study Finds Largest Set of Genes Related to Major Risk Factor for Heart Disease

基因组图谱研究发现最大一组与心脏病首要风险因素相关的基因

译者: Docofsoul

ScienceDaily (Aug. 5, 2010) — Scanning the genomes of more than 100,000 people from all over the world, scientists report the largest set of genes discovered underlying high cholesterol and high triglycerides -- the major risk factors for coronary heart disease, the nation's number one killer. Taken together, the gene variants explain between a quarter and a third of the inherited portions of cholesterol and triglyceride measured in the blood.

《每日科学》2010年8月5日报道 —— 科学家在扫描来自世界各地的超过10万人的基因组的基础上，发现了导致高胆固醇与高甘油三酸酯的最大一组基因。冠心病是美国人口的一号杀手，而高胆固醇与高甘油三酸酯则是导致冠心病的首要危险因素。总的来看，这一组基因变异解释了四分之一到三分之一左右的经由血液检测的胆固醇与甘油三酸酯的受遗传控制的那部分（的相关机制）。




Human heart illustration. (Credit: iStockphoto/Sebastian Kaulitzki)

图示：人类心脏（图片来源：iStockphoto/Sebastian Kaulitzki）

The research, representing scientists from 17 countries, appears in two papers in the Aug. 5 issue of Nature.

这是来自17个国家的科学家共同研究的工作成果。该成果分两篇论文发表于《Nature》八月五号这一期。

The National Institutes Of Health's National Heart, Lung, and Blood Institute (NHLBI) is the lead funder of the research, with additional support from the National Human Genome Research Institute (NHGRI), the National Institute on Aging (NIA), and several other NIH components.

国家卫生研究院（NIH）所属的国家心肺血液研究院（NHLBI）是本研究的主要资金支持者。此外，国家人类基因组研究院（NHGRI）与国家衰老研究院（NIA）以及NIH所属的几家单位也支持了这一研究。

Genome-wide association studies, or GWAS, analyze DNA across populations to pinpoint hard-to-find genetic hotspots for common diseases that are thought to have many causes, both genetic and environmental. Previous gene-scanning approaches have turned up hints about the nature of inherited heart disease risk. The new results take science well beyond what was previously known, and pinpoint research directions to elucidate the molecular and cellular mechanisms by which genetic variants contribute to disease.

全基因组关联研究，或称之为GWAS，旨在分析人口中的DNA以便为多病因（同时涉及遗传与环境）的普通疾病确认其它方法难以发现的相关遗传热点。此前的基因扫描方法已经揭示有关遗传性心脏病风险的性质的线索。而新的研究结果则极大地提高了相关领域的科学知识水平， 明确了最终阐释遗传变异所导致的相关疾病的分子机制与细胞机制这一研究方向。

"Genetic studies that survey a wide variety of human populations are a powerful tool for identifying hereditary factors in health and disease," said study co-author and NIH Director Francis S. Collins, M.D., Ph.D. "These results help refine our course for preventing and treating heart disease, a health problem that affects millions of Americans and many more people worldwide."

“基于大规模人口调查的遗传研究是证实健康与疾病的先天因素的强有力的工具。 心脏病影响了数百万美国人与世界各地许许多多的人们， 而这些研究结果将使预防与治疗心脏病的方向更加明朗、道路更为平坦。” 国家卫生研究院院长、医学博士、哲学博士Francis S. Collins说。

The research team found 95 genetic variants -- arrangements of the nucleic acids in DNA that differ among people -- which contribute to changes in blood cholesterol and triglyceride levels in women and men of many ethnic backgrounds. Abnormal levels of blood cholesterol and of triglycerides are powerful risk factors for heart disease. Because high blood cholesterol on its own does not cause symptoms, doctors routinely do blood tests to assess individual risk, but they do not know how much risk of developing cardiovascular disease is inherited.

该研究团队发现了95种遗传变异 —— DNA中的核酸排列（人与人之间的这种排列有差异）—— 这些变异与各种种族背景的男女性的血液胆固醇与甘油三酸酯水平直接相关。血液胆固醇与甘油三酸酯水平的异常是心脏病的强力危险因素。 因为高血液胆固醇本身并不引起症状，因此医生通常对血液进行常规检测以评估个体风险，但他们并不不解遗传因素在罹患心血管疾病风险方面所占据的相关比重。

Of the genetic variants, 59 had not been known and thus provide new clues for developing effective medicines to combat heart disease.

在95种遗传变异中，有59种为此前所未知，现在被撩开面纱，则必将为开发有效的药物来抗击心脏病提供新的线索。

A significant insight from this research is that many of the variants show up in the DNA of people of widely diverse backgrounds. That is because the scientists scoured the DNA from people participating in large, population-based heart disease studies, reflecting people of European, Eastern and Southern Asian, and African-American descent.

来自本研究的一个理解上的重大突破是：许多变异在背景极为广泛的人群的DNA中出现。这是因为这些科学家彻查了基于大规模人口的大型心脏病研究的参与者的DNA，反映了欧裔、东南亚裔与非洲-美洲裔血统背景参与者的实际情况。

Together, research participants from NHLBI study populations contributed about half of the 100,000 genomes scanned. Among the NIH population-based studies involved in the research were the Framingham Heart Study; the Atherosclerosis Risk in Communities Study; the Cardiovascular Health Study; the SardiNIA Study; the Ages, Gene, Environment Study; the InCHIANTI Study; the Family Heart Study; the NHLBI Candidate Gene Association Resource Program; the NIH Pharmacogenetics Research Network; the deCODE MI Study; and the Women's Genome Health Study.

总的来说，所扫描的10万个基因组有一半来自NHLBI研究中的参与者。与本研究相关的NIH人群调查研究中，有弗拉明翰心脏研究（the Framingham Heart Study）、心血管健康研究（the Cardiovascular Health Study）、SardiNIA研究（the SardiNIA Study）、“年龄、基因、环境”研究（the Ages, Gene, Environment Study）、the InCHIANTI Study、家庭心脏研究（the Family Heart Study）、NHLBI候选基因关联资源计划（the NHLBI Candidate Gene Association Resource Program）、国家卫生研究院遗传药理学研究网络（the NIH Pharmacogenetics Research Network）、the deCODE MI Study与妇女基因组健康研究（the deCODE MI Study;）。

"The NHLBI is a leader in supporting long-term studies, including the decades-long Framingham Heart Study, that carefully track the health outcomes of large groups of people and generations of families." said NHLBI Acting Director Susan B. Shurin, M.D. "This genome-wide association study successfully demonstrates how cutting-edge genomics research can be leveraged by our past and current research investment in population-based studies assessing long-term health and disease."

“NHLBI在支持长期研究项目方面是个领导者，这些项目包括对大批人群及其家庭几代人的健康后果进行严密细致的长达几十年的随访的弗拉明翰心脏研究.。这一全基因组关联研究成功地证明了：尖端基因组学研究可受到我们过去与目前的旨在评估长期健康与疾病的大规模人群研究的时间与精力等投入的影响；并且也成功证明了这个影响的相关程度。” NHLBI代理主任、医学博士Susan B. Shurin说。

The research team's other study probed deeply into one of the genetic variants identified in the accompanying GWAS analysis.

该研究团队的另外一个研究则深入探索了附随的GWAS分析研究中所证实的遗传变异中的一个变异情形。.

In the group's second study, the scientists had an unusual opportunity to follow up on the findings of the GWAS to determining how one unusual gene variant trips up cholesterol and triglyceride metabolism in mice. Previous studies had identified the same genetic variant in humans who were prone to deadly heart attacks: The variant is common in people of African American, Hispanic, Asian Indian, and Chinese ancestries. Having a genetically identical mouse model enables researchers to look further into the contribution of a particular genetic variant to inherited heart disease risk.

在该研究团体的第二个研究中，科学家们获得一次非同寻常的机遇， 对GWAS的发现进行了随访，以查明一个独特的基因变异导致小鼠胆固醉与甘油三酸酯代谢的异常的作用过程。此前研究已证实相同的人类遗传变异有导致致命的心脏病发作：这种变异在非裔美国人、西班牙人、亚裔印度人与中国人的祖先中相当普遍。有了遗传学上对等的小鼠模型，研究者得以对一种特定的遗传变异对遗传性心脏病风险的影响一探究竟。

"The new findings point us to specific genetic signposts that allow us to understand more fully why many people from all walks of life have abnormal levels of cholesterol and other blood lipids that lead to heart disease," said Christopher J. O'Donnell, M.D., associate director of the Framingham Heart Study and senior advisor for genomics to the NHLBI acting director. "What's really exciting about this work is that we are moving from discovery to understanding brand-new information about how genes alter the lipids that contribute to heart disease."

“新的发现为我们指明特定的遗传路标， 从而允许我们更全面地理解为何来自各个行业的许多人们有着可导致心脏病的异常水平的胆固醇与其它血液脂质。本研究工作的真正令人激动的地方是：在基因改变与心脏病有关的脂质的具体过程方面，我们正在从探索发现转向理解全新的信息的方向前进。” 医学博士、弗拉明翰心脏研究计划副主任、为NHLBI代理主任提供有关基因组学咨询的资深顾问Christopher J. O'Donnell说。

In addition to the NHLBI, the NIA and the NHGRI, other NIH funding sources include the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Research Resources.

除了NHLBI，NIA与NHGRI，其它NIH基金来源包括：国立糖尿病消化与肾病研究所、国家神经疾病和中风研究所、国立癌症研究所、国立普通医学科学研究所、国立过敏症和传染病研究所、尤尼斯•肯尼迪•史瑞沃国家儿童健康与人类发展协会与国家研究资源中心。

（Docofsoul 译于2010-8-8）

=============================================================================

基因组图谱研究发现最大一组与心脏病首要风险因素相关的基因

译者: Docofsoul

《每日科学》2010年8月5日报道 —— 科学家在扫描来自世界各地的超过10万人的基因组的基础上，发现了导致高胆固醇与高甘油三酸酯的最大一组基因。冠心病是美国人口的一号杀手，而高胆固醇与高甘油三酸酯则是导致冠心病的首要危险因素。总的来看，这一组基因变异解释了四分之一到三分之一左右的经由血液检测的胆固醇与甘油三酸酯的受遗传控制的那部分（的相关机制）。


图示：人类心脏（图片来源：iStockphoto/Sebastian Kaulitzki）

这是来自17个国家的科学家共同研究的工作成果。该成果分两篇论文发表于《Nature》八月五号这一期。

国家卫生研究院（NIH）所属的国家心肺血液研究院（NHLBI）是本研究的主要资金支持者。此外，国家人类基因组研究院（NHGRI）与国家衰老研究院（NIA）以及NIH所属的几家单位也支持了这一研究。

全基因组关联研究，或称之为GWAS，旨在分析人口中的DNA以便为多病因（同时涉及遗传与环境）的普通疾病确认其它方法难以发现的相关遗传热点。此前的基因扫描方法已经揭示有关遗传性心脏病风险的性质的线索。而新的研究结果则极大地提高了相关领域的科学知识水平， 明确了最终阐释遗传变异所导致的相关疾病的分子机制与细胞机制这一研究方向。

“基于大规模人口调查的遗传研究是证实健康与疾病的先天因素的强有力的工具。 心脏病影响了数百万美国人与世界各地许许多多的人们， 而这些研究结果将使预防与治疗心脏病的方向更加明朗、道路更为平坦。” 国家卫生研究院院长、医学博士、哲学博士Francis S. Collins说。

该研究团队发现了95种遗传变异 —— DNA中的核酸排列（人与人之间的这种排列有差异）—— 这些变异与各种种族背景的男女性的血液胆固醇与甘油三酸酯水平直接相关。血液胆固醇与甘油三酸酯水平的异常是心脏病的强力危险因素。 因为高血液胆固醇本身并不引起症状，因此医生通常对血液进行常规检测以评估个体风险，但他们并不不解遗传因素在罹患心血管疾病风险方面所占据的相关比重。

在95种遗传变异中，有59种为此前所未知，现在被撩开面纱，则必将为开发有效的药物来抗击心脏病提供新的线索。

来自本研究的一个理解上的重大突破是：许多变异在背景极为广泛的人群的DNA中出现。这是因为这些科学家彻查了基于大规模人口的大型心脏病研究的参与者的DNA，反映了欧裔、东南亚裔与非洲-美洲裔血统背景参与者的实际情况。

总的来说，所扫描的10万个基因组有一半来自NHLBI研究中的参与者。与本研究相关的NIH人群调查研究中，有弗拉明翰心脏研究（the Framingham Heart Study）、心血管健康研究（the Cardiovascular Health Study）、SardiNIA研究（the SardiNIA Study）、“年龄、基因、环境”研究（the Ages, Gene, Environment Study）、the InCHIANTI Study、家庭心脏研究（the Family Heart Study）、NHLBI候选基因关联资源计划（the NHLBI Candidate Gene Association Resource Program）、国家卫生研究院遗传药理学研究网络（the NIH Pharmacogenetics Research Network）、the deCODE MI Study与妇女基因组健康研究（the deCODE MI Study;）。

“NHLBI在支持长期研究项目方面是个领导者，这些项目包括对大批人群及其家庭几代人的健康后果进行严密细致的长达几十年的随访的弗拉明翰心脏研究.。这一全基因组关联研究成功地证明了：尖端基因组学研究可受到我们过去与目前的旨在评估长期健康与疾病的大规模人群研究的时间与精力等投入的影响；并且也成功证明了这个影响的相关程度。” NHLBI代理主任、医学博士Susan B. Shurin说。

该研究团队的另外一个研究则深入探索了附随的GWAS分析研究中所证实的遗传变异中的一个变异情形。.

在该研究团体的第二个研究中，科学家们获得一次非同寻常的机遇， 对GWAS的发现进行了随访，以查明一个独特的基因变异导致小鼠胆固醉与甘油三酸酯代谢的异常的作用过程。此前研究已证实相同的人类遗传变异有导致致命的心脏病发作：这种变异在非裔美国人、西班牙人、亚裔印度人与中国人的祖先中相当普遍。有了遗传学上对等的小鼠模型，研究者得以对一种特定的遗传变异对遗传性心脏病风险的影响一探究竟。

“新的发现为我们指明特定的遗传路标， 从而允许我们更全面地理解为何来自各个行业的许多人们有着可导致心脏病的异常水平的胆固醇与其它血液脂质。本研究工作的真正令人激动的地方是：在基因改变与心脏病有关的脂质的具体过程方面，我们正在从探索发现转向理解全新的信息的方向前进。” 医学博士、弗拉明翰心脏研究计划副主任、为NHLBI代理主任提供有关基因组学咨询的资深顾问Christopher J. O'Donnell说。

除了NHLBI，NIA与NHGRI，其它NIH基金来源包括：国立糖尿病消化与肾病研究所、国家神经疾病和中风研究所、国立癌症研究所、国立普通医学科学研究所、国立过敏症和传染病研究所、尤尼斯•肯尼迪•史瑞沃国家儿童健康与人类发展协会与国家研究资源中心。