Antithrombin, protein C, and protein S: genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels
Background: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
27 Apr 2023
|
| In: |
Arteriosclerosis, thrombosis, and vascular biology
Year: 2023, Jahrgang: 43, Heft: 7, Pages: e254-e269 |
| ISSN: | 1524-4636 |
| DOI: | 10.1161/ATVBAHA.122.318213 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1161/ATVBAHA.122.318213 Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318213 
|
| Verfasserangaben: | Yuekai Ji, Gerard Temprano-Sagrera, Lori A. Holle, Allison Bebo, Jennifer A. Brody, Ngoc-Quynh Le, Kadri Kangro, Michael R. Brown, Angel Martinez-Perez, Colleen M. Sitlani, Pierre Suchon, Marcus E. Kleber, David B. Emmert, Ayse Bilge Ozel, Dre’Von A. Dobson, Weihong Tang, Dolors Llobet, Russell P. Tracy, Jean-François Deleuze, Graciela E. Delgado, Martin Gögele, Kerri L. Wiggins, Juan Carlos Souto, James S. Pankow, Kent D. Taylor, David-Alexandre Trégouët, Angela P. Moissl, Christian Fuchsberger, Frits R. Rosendaal, Alanna C. Morrison, Jose Manuel Soria, Mary Cushman, Pierre-Emmanuel Morange, Winfried März, Andrew A. Hicks, Karl C. Desch, Andrew D. Johnson, Paul S. de Vries, CHARGE Consortium Hemostasis Working Group, INVENT Consortium, Alisa S. Wolberg, Nicholas L. Smith, Maria Sabater-Lleal |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1858263468 | ||
| 003 | DE-627 | ||
| 005 | 20240307055116.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230830s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/ATVBAHA.122.318213 |2 doi | |
| 035 | |a (DE-627)1858263468 | ||
| 035 | |a (DE-599)KXP1858263468 | ||
| 035 | |a (OCoLC)1425212393 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Ji, Yuekai |e VerfasserIn |0 (DE-588)1300485248 |0 (DE-627)1858264553 |4 aut | |
| 245 | 1 | 0 | |a Antithrombin, protein C, and protein S |b genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels |c Yuekai Ji, Gerard Temprano-Sagrera, Lori A. Holle, Allison Bebo, Jennifer A. Brody, Ngoc-Quynh Le, Kadri Kangro, Michael R. Brown, Angel Martinez-Perez, Colleen M. Sitlani, Pierre Suchon, Marcus E. Kleber, David B. Emmert, Ayse Bilge Ozel, Dre’Von A. Dobson, Weihong Tang, Dolors Llobet, Russell P. Tracy, Jean-François Deleuze, Graciela E. Delgado, Martin Gögele, Kerri L. Wiggins, Juan Carlos Souto, James S. Pankow, Kent D. Taylor, David-Alexandre Trégouët, Angela P. Moissl, Christian Fuchsberger, Frits R. Rosendaal, Alanna C. Morrison, Jose Manuel Soria, Mary Cushman, Pierre-Emmanuel Morange, Winfried März, Andrew A. Hicks, Karl C. Desch, Andrew D. Johnson, Paul S. de Vries, CHARGE Consortium Hemostasis Working Group, INVENT Consortium, Alisa S. Wolberg, Nicholas L. Smith, Maria Sabater-Lleal |
| 264 | 1 | |c 27 Apr 2023 | |
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Originally published 27 Apr 2023 | ||
| 500 | |a Gesehen am 30.08.2023 | ||
| 520 | |a Background: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total. Methods: Study participants were of European and African ancestries, and genotype data were imputed to TOPMed, a dense multiancestry reference panel. Each of the 10 studies conducted a genome-wide association studies for each phenotype and summary results were meta-analyzed, stratified by ancestry. Analysis of antithrombin included 25 243 European ancestry and 2688 African ancestry participants, PC analysis included 16 597 European ancestry and 2688 African ancestry participants, PSF and PST analysis included 4113 and 6409 European ancestry participants. We also conducted transcriptome-wide association analyses and multiphenotype analysis to discover additional associations. Novel genome-wide association studies and transcriptome-wide association analyses findings were validated by in vitro functional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes. Results: Genome-wide association studies meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (GCKR, BAZ1B, and HP-TXNL4B) and 1 with PS levels (ORM1-ORM2). transcriptome-wide association analyses identified 3 newly associated genes: 1 with antithrombin level (FCGRT), 1 with PC (GOLM2), and 1 with PS (MYL7). In addition, we replicated 7 independent loci reported in previous studies. Functional experiments provided evidence for the involvement of GCKR, SNX17, and HP genes in antithrombin regulation. Conclusions: The use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels. | ||
| 650 | 4 | |a anticoagulant | |
| 650 | 4 | |a antithrombin | |
| 650 | 4 | |a genome-wide association study | |
| 650 | 4 | |a genotype | |
| 650 | 4 | |a hemostasis | |
| 650 | 4 | |a protein C | |
| 650 | 4 | |a protein S | |
| 700 | 1 | |a Temprano-Sagrera, Gerard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Holle, Lori A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bebo, Allison |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brody, Jennifer A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Le, Ngoc-Quynh |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kangro, Kadri |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brown, Michael R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Martinez-Perez, Angel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sitlani, Colleen M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Suchon, Pierre |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kleber, Marcus E. |d 1974- |e VerfasserIn |0 (DE-588)1030135177 |0 (DE-627)734830440 |0 (DE-576)377941379 |4 aut | |
| 700 | 1 | |a Emmert, David B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bilge Ozel, Ayse |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dobson, Dre’Von A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tang, Weihong |e VerfasserIn |4 aut | |
| 700 | 1 | |a Llobet, Dolors |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tracy, Russell P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Deleuze, Jean-François |e VerfasserIn |4 aut | |
| 700 | 1 | |a Delgado Gonzales de Kleber, Graciela |d 1960- |e VerfasserIn |0 (DE-588)1070236403 |0 (DE-627)823400379 |0 (DE-576)429882386 |4 aut | |
| 700 | 1 | |a Gögele, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wiggins, Kerri L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Souto, Juan Carlos |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pankow, James S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Taylor, Kent D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trégouët, David-Alexandre |e VerfasserIn |4 aut | |
| 700 | 1 | |a Moissl-Blanke, Angela P. |d 1984- |e VerfasserIn |0 (DE-588)1192773756 |0 (DE-627)1671247248 |4 aut | |
| 700 | 1 | |a Fuchsberger, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rosendaal, Frits R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Morrison, Alanna C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Soria, Jose Manuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cushman, Mary |e VerfasserIn |4 aut | |
| 700 | 1 | |a Morange, Pierre-Emmanuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a März, Winfried |d 1958- |e VerfasserIn |0 (DE-588)1027603599 |0 (DE-627)729463605 |0 (DE-576)373454635 |4 aut | |
| 700 | 1 | |a Hicks, Andrew A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Desch, Karl C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Johnson, Andrew D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a de Vries, Paul S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a null, null |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wolberg, Alisa S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Smith, Nicholas L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sabater-Lleal, Maria |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Arteriosclerosis, thrombosis, and vascular biology |d Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1995 |g 43(2023), 7 vom: Juli, Seite e254-e269 |h Online-Ressource |w (DE-627)303389079 |w (DE-600)1494427-3 |w (DE-576)080860516 |x 1524-4636 |7 nnas |a Antithrombin, protein C, and protein S genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels |
| 773 | 1 | 8 | |g volume:43 |g year:2023 |g number:7 |g month:07 |g pages:e254-e269 |g extent:16 |a Antithrombin, protein C, and protein S genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels |
| 856 | 4 | 0 | |u https://doi.org/10.1161/ATVBAHA.122.318213 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318213 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230830 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1027603599 |a März, Winfried |m 1027603599:März, Winfried |d 60000 |d 61400 |e 60000PM1027603599 |e 61400PM1027603599 |k 0/60000/ |k 1/60000/61400/ |p 34 | ||
| 998 | |g 1192773756 |a Moissl-Blanke, Angela P. |m 1192773756:Moissl-Blanke, Angela P. |d 60000 |d 61400 |e 60000PM1192773756 |e 61400PM1192773756 |k 0/60000/ |k 1/60000/61400/ |p 27 | ||
| 998 | |g 1070236403 |a Delgado Gonzales de Kleber, Graciela |m 1070236403:Delgado Gonzales de Kleber, Graciela |d 60000 |d 61400 |e 60000PD1070236403 |e 61400PD1070236403 |k 0/60000/ |k 1/60000/61400/ |p 20 | ||
| 998 | |g 1030135177 |a Kleber, Marcus E. |m 1030135177:Kleber, Marcus E. |d 60000 |d 61400 |e 60000PK1030135177 |e 61400PK1030135177 |k 0/60000/ |k 1/60000/61400/ |p 12 | ||
| 999 | |a KXP-PPN1858263468 |e 4371087531 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedDisp":"27 Apr 2023","dateIssuedKey":"2023"}],"note":["Originally published 27 Apr 2023","Gesehen am 30.08.2023"],"recId":"1858263468","name":{"displayForm":["Yuekai Ji, Gerard Temprano-Sagrera, Lori A. Holle, Allison Bebo, Jennifer A. Brody, Ngoc-Quynh Le, Kadri Kangro, Michael R. Brown, Angel Martinez-Perez, Colleen M. Sitlani, Pierre Suchon, Marcus E. Kleber, David B. Emmert, Ayse Bilge Ozel, Dre’Von A. Dobson, Weihong Tang, Dolors Llobet, Russell P. Tracy, Jean-François Deleuze, Graciela E. Delgado, Martin Gögele, Kerri L. Wiggins, Juan Carlos Souto, James S. Pankow, Kent D. Taylor, David-Alexandre Trégouët, Angela P. Moissl, Christian Fuchsberger, Frits R. Rosendaal, Alanna C. Morrison, Jose Manuel Soria, Mary Cushman, Pierre-Emmanuel Morange, Winfried März, Andrew A. Hicks, Karl C. Desch, Andrew D. Johnson, Paul S. de Vries, CHARGE Consortium Hemostasis Working Group, INVENT Consortium, Alisa S. Wolberg, Nicholas L. Smith, Maria Sabater-Lleal"]},"title":[{"subtitle":"genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levels","title":"Antithrombin, protein C, and protein S","title_sort":"Antithrombin, protein C, and protein S"}],"relHost":[{"origin":[{"dateIssuedDisp":"1995-","publisher":"Lippincott, Williams & Wilkins ; HighWire","publisherPlace":"Philadelphia, Pa. ; Stanford, Calif.","dateIssuedKey":"1995"}],"recId":"303389079","part":{"pages":"e254-e269","issue":"7","text":"43(2023), 7 vom: Juli, Seite e254-e269","volume":"43","extent":"16","year":"2023"},"pubHistory":["Vol. 15, no. 1 (January 1995)-"],"id":{"zdb":["1494427-3"],"issn":["1524-4636"],"eki":["303389079"]},"type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Antithrombin, protein C, and protein S genome and transcriptome-wide association studies identify 7 novel loci regulating plasma levelsArteriosclerosis, thrombosis, and vascular biology","note":["Gesehen am 18.08.25"],"title":[{"subtitle":"journal of the American Heart Association","title":"Arteriosclerosis, thrombosis, and vascular biology","title_sort":"Arteriosclerosis, thrombosis, and vascular biology"}],"physDesc":[{"extent":"Online-Ressource"}],"language":["eng"]}],"physDesc":[{"extent":"16 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"eki":["1858263468"],"doi":["10.1161/ATVBAHA.122.318213"]},"person":[{"role":"aut","display":"Ji, Yuekai","given":"Yuekai","family":"Ji"},{"given":"Gerard","family":"Temprano-Sagrera","role":"aut","display":"Temprano-Sagrera, Gerard"},{"family":"Holle","given":"Lori A.","display":"Holle, Lori A.","role":"aut"},{"family":"Bebo","given":"Allison","display":"Bebo, Allison","role":"aut"},{"display":"Brody, Jennifer A.","role":"aut","family":"Brody","given":"Jennifer A."},{"family":"Le","given":"Ngoc-Quynh","display":"Le, Ngoc-Quynh","role":"aut"},{"given":"Kadri","family":"Kangro","role":"aut","display":"Kangro, Kadri"},{"display":"Brown, Michael R.","role":"aut","family":"Brown","given":"Michael R."},{"family":"Martinez-Perez","given":"Angel","display":"Martinez-Perez, Angel","role":"aut"},{"display":"Sitlani, Colleen M.","role":"aut","family":"Sitlani","given":"Colleen M."},{"display":"Suchon, Pierre","role":"aut","family":"Suchon","given":"Pierre"},{"given":"Marcus E.","family":"Kleber","role":"aut","display":"Kleber, Marcus E."},{"role":"aut","display":"Emmert, David B.","given":"David B.","family":"Emmert"},{"display":"Bilge Ozel, Ayse","role":"aut","family":"Bilge Ozel","given":"Ayse"},{"role":"aut","display":"Dobson, Dre’Von A.","given":"Dre’Von A.","family":"Dobson"},{"given":"Weihong","family":"Tang","role":"aut","display":"Tang, Weihong"},{"display":"Llobet, Dolors","role":"aut","family":"Llobet","given":"Dolors"},{"given":"Russell P.","family":"Tracy","role":"aut","display":"Tracy, Russell P."},{"role":"aut","display":"Deleuze, Jean-François","given":"Jean-François","family":"Deleuze"},{"family":"Delgado Gonzales de Kleber","given":"Graciela","display":"Delgado Gonzales de Kleber, Graciela","role":"aut"},{"role":"aut","display":"Gögele, Martin","given":"Martin","family":"Gögele"},{"given":"Kerri L.","family":"Wiggins","role":"aut","display":"Wiggins, Kerri L."},{"family":"Souto","given":"Juan Carlos","display":"Souto, Juan Carlos","role":"aut"},{"role":"aut","display":"Pankow, James S.","given":"James S.","family":"Pankow"},{"display":"Taylor, Kent D.","role":"aut","family":"Taylor","given":"Kent D."},{"given":"David-Alexandre","family":"Trégouët","role":"aut","display":"Trégouët, David-Alexandre"},{"given":"Angela P.","family":"Moissl-Blanke","role":"aut","display":"Moissl-Blanke, Angela P."},{"display":"Fuchsberger, Christian","role":"aut","family":"Fuchsberger","given":"Christian"},{"role":"aut","display":"Rosendaal, Frits R.","given":"Frits R.","family":"Rosendaal"},{"family":"Morrison","given":"Alanna C.","display":"Morrison, Alanna C.","role":"aut"},{"family":"Soria","given":"Jose Manuel","display":"Soria, Jose Manuel","role":"aut"},{"display":"Cushman, Mary","role":"aut","family":"Cushman","given":"Mary"},{"role":"aut","display":"Morange, Pierre-Emmanuel","given":"Pierre-Emmanuel","family":"Morange"},{"display":"März, Winfried","role":"aut","family":"März","given":"Winfried"},{"family":"Hicks","given":"Andrew A.","display":"Hicks, Andrew A.","role":"aut"},{"display":"Desch, Karl C.","role":"aut","family":"Desch","given":"Karl C."},{"family":"Johnson","given":"Andrew D.","display":"Johnson, Andrew D.","role":"aut"},{"given":"Paul S.","family":"de Vries","role":"aut","display":"de Vries, Paul S."},{"family":"null","given":"null","display":"null, null","role":"aut"},{"display":"Wolberg, Alisa S.","role":"aut","family":"Wolberg","given":"Alisa S."},{"given":"Nicholas L.","family":"Smith","role":"aut","display":"Smith, Nicholas L."},{"family":"Sabater-Lleal","given":"Maria","display":"Sabater-Lleal, Maria","role":"aut"}],"language":["eng"]} | ||
| SRT | |a JIYUEKAITEANTITHROMB2720 | ||