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Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 110, 2013, 2, S. 588-593 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David |
|---|---|
| author |
Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David |
| spellingShingle |
Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David Proceedings of the National Academy of Sciences Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association Multidisciplinary |
| author_sort |
desch, karl c. |
| spelling |
Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1219885110 <jats:p>The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (<jats:italic>n</jats:italic>= 1,152 and<jats:italic>n</jats:italic>= 2,310) and identified signals at<jats:italic>ABO</jats:italic>(<jats:italic>P</jats:italic>< 7.9E-139) and<jats:italic>VWF</jats:italic>(<jats:italic>P</jats:italic>< 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12–2p13 (LOD score 5.3) and at the<jats:italic>ABO</jats:italic>locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the “missing heritability” for other complex genetic traits.</jats:p> Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association Proceedings of the National Academy of Sciences |
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| title |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_unstemmed |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_full |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_fullStr |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_full_unstemmed |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_short |
Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_sort |
linkage analysis identifies a locus for plasma von willebrand factor undetected by genome-wide association |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.1219885110 |
| publishDate |
2013 |
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588-593 |
| description |
<jats:p>The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (<jats:italic>n</jats:italic>= 1,152 and<jats:italic>n</jats:italic>= 2,310) and identified signals at<jats:italic>ABO</jats:italic>(<jats:italic>P</jats:italic>< 7.9E-139) and<jats:italic>VWF</jats:italic>(<jats:italic>P</jats:italic>< 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12–2p13 (LOD score 5.3) and at the<jats:italic>ABO</jats:italic>locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the “missing heritability” for other complex genetic traits.</jats:p> |
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| author | Desch, Karl C., Ozel, Ayse B., Siemieniak, David, Kalish, Yossi, Shavit, Jordan A., Thornburg, Courtney D., Sharathkumar, Anjali A., McHugh, Caitlin P., Laurie, Cathy C., Crenshaw, Andrew, Mirel, Daniel B., Kim, Yoonhee, Cropp, Cheryl D., Molloy, Anne M., Kirke, Peadar N., Bailey-Wilson, Joan E., Wilson, Alexander F., Mills, James L., Scott, John M., Brody, Lawrence C., Li, Jun Z., Ginsburg, David |
| author_facet | Desch, Karl C., Ozel, Ayse B., Siemieniak, David, Kalish, Yossi, Shavit, Jordan A., Thornburg, Courtney D., Sharathkumar, Anjali A., McHugh, Caitlin P., Laurie, Cathy C., Crenshaw, Andrew, Mirel, Daniel B., Kim, Yoonhee, Cropp, Cheryl D., Molloy, Anne M., Kirke, Peadar N., Bailey-Wilson, Joan E., Wilson, Alexander F., Mills, James L., Scott, John M., Brody, Lawrence C., Li, Jun Z., Ginsburg, David, Desch, Karl C., Ozel, Ayse B., Siemieniak, David, Kalish, Yossi, Shavit, Jordan A., Thornburg, Courtney D., Sharathkumar, Anjali A., McHugh, Caitlin P., Laurie, Cathy C., Crenshaw, Andrew, Mirel, Daniel B., Kim, Yoonhee, Cropp, Cheryl D., Molloy, Anne M., Kirke, Peadar N., Bailey-Wilson, Joan E., Wilson, Alexander F., Mills, James L., Scott, John M., Brody, Lawrence C., Li, Jun Z., Ginsburg, David |
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| description | <jats:p>The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (<jats:italic>n</jats:italic>= 1,152 and<jats:italic>n</jats:italic>= 2,310) and identified signals at<jats:italic>ABO</jats:italic>(<jats:italic>P</jats:italic>< 7.9E-139) and<jats:italic>VWF</jats:italic>(<jats:italic>P</jats:italic>< 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12–2p13 (LOD score 5.3) and at the<jats:italic>ABO</jats:italic>locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the “missing heritability” for other complex genetic traits.</jats:p> |
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| institution | DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3 |
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| spelling | Desch, Karl C. Ozel, Ayse B. Siemieniak, David Kalish, Yossi Shavit, Jordan A. Thornburg, Courtney D. Sharathkumar, Anjali A. McHugh, Caitlin P. Laurie, Cathy C. Crenshaw, Andrew Mirel, Daniel B. Kim, Yoonhee Cropp, Cheryl D. Molloy, Anne M. Kirke, Peadar N. Bailey-Wilson, Joan E. Wilson, Alexander F. Mills, James L. Scott, John M. Brody, Lawrence C. Li, Jun Z. Ginsburg, David 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1219885110 <jats:p>The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (<jats:italic>n</jats:italic>= 1,152 and<jats:italic>n</jats:italic>= 2,310) and identified signals at<jats:italic>ABO</jats:italic>(<jats:italic>P</jats:italic>< 7.9E-139) and<jats:italic>VWF</jats:italic>(<jats:italic>P</jats:italic>< 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12–2p13 (LOD score 5.3) and at the<jats:italic>ABO</jats:italic>locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the “missing heritability” for other complex genetic traits.</jats:p> Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association Proceedings of the National Academy of Sciences |
| spellingShingle | Desch, Karl C., Ozel, Ayse B., Siemieniak, David, Kalish, Yossi, Shavit, Jordan A., Thornburg, Courtney D., Sharathkumar, Anjali A., McHugh, Caitlin P., Laurie, Cathy C., Crenshaw, Andrew, Mirel, Daniel B., Kim, Yoonhee, Cropp, Cheryl D., Molloy, Anne M., Kirke, Peadar N., Bailey-Wilson, Joan E., Wilson, Alexander F., Mills, James L., Scott, John M., Brody, Lawrence C., Li, Jun Z., Ginsburg, David, Proceedings of the National Academy of Sciences, Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association, Multidisciplinary |
| title | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_full | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_fullStr | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_full_unstemmed | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_short | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| title_sort | linkage analysis identifies a locus for plasma von willebrand factor undetected by genome-wide association |
| title_unstemmed | Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.1219885110 |