Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities

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Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities. / Shadrina, Alexandra S.; Elgaeva, Elizaveta E.; Stanaway, Ian B. et al.

In: PLoS ONE, Vol. 17, No. 5, e0268725, 05.2022.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{19c04a331ee64858a82f26cdd6c634ef,

title = "Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities",

abstract = "Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study. We conducted MR analysis using a fixed effects inverse-variance weighted meta-analysis of Wald ratios method. For MICB and CD209, we used data from a large-scale genome-wide association study (GWAS) for plasma protein levels (N = 3,301). For VVs, we used GWAS data obtained in the FinnGen project (N = 128,698), the eMERGE network (phase 3, N = 48,429), and the UK Biobank data available in the Gene ATLAS (N = 452,264). The data used in the study were obtained in individuals of European descent. The results for MICB did not pass criteria for statistical significance and replication. The results for CD209 passed all statistical significance thresholds, indicating that the genetically predicted increase in CD209 level is associated with increased risk of VVs (βMR (SE) = 0.07 (0.01), OR (95% CI) = 1.08 (1.05–1.10), P-value = 5.9 ×10−11 in the meta-analysis of three cohorts). Our findings provide further support that CD209 can potentially be involved in VVs. In future studies, independent validation of our results using data from more powerful GWASs for CD209 measured by different methods would be beneficial.",

keywords = "Genome-Wide Association Study, Humans, Lower Extremity/pathology, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Varicose Veins/genetics",

author = "Shadrina, {Alexandra S.} and Elgaeva, {Elizaveta E.} and Stanaway, {Ian B.} and Jarvik, {Gail P.} and Bahram Namjou and Wei, {Wei Qi} and Joe Glessner and Hakon Hakonarson and Pradeep Suri and Tsepilov, {Yakov A.}",

note = "Funding Information: The work of ASSh, EEE, and YAT was supported by the Russian Ministry of Education and Science under the 5-100 Excellence Programme and by the Ministry of Education and Science of the RF via the Institute of Cytology and Genetics (project #FWNR-2022-0020). Dr. Suri is a Staff Physician at the VA Puget Sound Health Care System. Dr. Stanaway{\textquoteright}s time was supported by the University of Washington Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research Resource Core. The CLEAR Center is a Core Center for Clinical Research (CCCR) funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health under Award Number P30AR072572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The eMERGE Network phase III was initiated and funded by NHGRI through the following grants: U01HG8657 (Group Health Cooperative/University of Washington); U01HG8685 (Brigham and Women{\textquoteright}s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children{\textquoteright}s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children{\textquoteright}s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). The content of this work is solely the responsibility of the authors and does not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We want to acknowledge the participants and investigators of FinnGen study (https://www.finngen.fi/en), the Gene ATLAS project (http://geneatlas.roslin.ed.ac.uk/), the human plasma proteome study (Sun B.B., et al., 2018; Genomic atlas of the human plasma proteome), and the eMERGE Network (https://emerge-network.org/) and thank them for providing genetic data that we have used in our study. We gratefully thank UK Biobank (http://www.ukbiobank.ac.uk/) for establishing a powerful resource for genetic and epidemiological studies. Publisher Copyright: Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.",

year = "2022",

month = may,

doi = "10.1371/journal.pone.0268725",

language = "English",

volume = "17",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

RIS

TY - JOUR

T1 - Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities

AU - Shadrina, Alexandra S.

AU - Elgaeva, Elizaveta E.

AU - Stanaway, Ian B.

AU - Jarvik, Gail P.

AU - Namjou, Bahram

AU - Wei, Wei Qi

AU - Glessner, Joe

AU - Hakonarson, Hakon

AU - Suri, Pradeep

AU - Tsepilov, Yakov A.

N1 - Funding Information: The work of ASSh, EEE, and YAT was supported by the Russian Ministry of Education and Science under the 5-100 Excellence Programme and by the Ministry of Education and Science of the RF via the Institute of Cytology and Genetics (project #FWNR-2022-0020). Dr. Suri is a Staff Physician at the VA Puget Sound Health Care System. Dr. Stanaway’s time was supported by the University of Washington Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research Resource Core. The CLEAR Center is a Core Center for Clinical Research (CCCR) funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health under Award Number P30AR072572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The eMERGE Network phase III was initiated and funded by NHGRI through the following grants: U01HG8657 (Group Health Cooperative/University of Washington); U01HG8685 (Brigham and Women’s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children’s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children’s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). The content of this work is solely the responsibility of the authors and does not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We want to acknowledge the participants and investigators of FinnGen study (https://www.finngen.fi/en), the Gene ATLAS project (http://geneatlas.roslin.ed.ac.uk/), the human plasma proteome study (Sun B.B., et al., 2018; Genomic atlas of the human plasma proteome), and the eMERGE Network (https://emerge-network.org/) and thank them for providing genetic data that we have used in our study. We gratefully thank UK Biobank (http://www.ukbiobank.ac.uk/) for establishing a powerful resource for genetic and epidemiological studies. Publisher Copyright: Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

PY - 2022/5

Y1 - 2022/5

N2 - Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study. We conducted MR analysis using a fixed effects inverse-variance weighted meta-analysis of Wald ratios method. For MICB and CD209, we used data from a large-scale genome-wide association study (GWAS) for plasma protein levels (N = 3,301). For VVs, we used GWAS data obtained in the FinnGen project (N = 128,698), the eMERGE network (phase 3, N = 48,429), and the UK Biobank data available in the Gene ATLAS (N = 452,264). The data used in the study were obtained in individuals of European descent. The results for MICB did not pass criteria for statistical significance and replication. The results for CD209 passed all statistical significance thresholds, indicating that the genetically predicted increase in CD209 level is associated with increased risk of VVs (βMR (SE) = 0.07 (0.01), OR (95% CI) = 1.08 (1.05–1.10), P-value = 5.9 ×10−11 in the meta-analysis of three cohorts). Our findings provide further support that CD209 can potentially be involved in VVs. In future studies, independent validation of our results using data from more powerful GWASs for CD209 measured by different methods would be beneficial.

AB - Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study. We conducted MR analysis using a fixed effects inverse-variance weighted meta-analysis of Wald ratios method. For MICB and CD209, we used data from a large-scale genome-wide association study (GWAS) for plasma protein levels (N = 3,301). For VVs, we used GWAS data obtained in the FinnGen project (N = 128,698), the eMERGE network (phase 3, N = 48,429), and the UK Biobank data available in the Gene ATLAS (N = 452,264). The data used in the study were obtained in individuals of European descent. The results for MICB did not pass criteria for statistical significance and replication. The results for CD209 passed all statistical significance thresholds, indicating that the genetically predicted increase in CD209 level is associated with increased risk of VVs (βMR (SE) = 0.07 (0.01), OR (95% CI) = 1.08 (1.05–1.10), P-value = 5.9 ×10−11 in the meta-analysis of three cohorts). Our findings provide further support that CD209 can potentially be involved in VVs. In future studies, independent validation of our results using data from more powerful GWASs for CD209 measured by different methods would be beneficial.

KW - Genome-Wide Association Study

KW - Humans

KW - Lower Extremity/pathology

KW - Mendelian Randomization Analysis

KW - Polymorphism, Single Nucleotide

KW - Varicose Veins/genetics

UR - http://www.scopus.com/inward/record.url?scp=85130495584&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e76f9a53-b092-3c4b-9946-9f0ae75cdbdd/

U2 - 10.1371/journal.pone.0268725

DO - 10.1371/journal.pone.0268725

M3 - Article

C2 - 35594287

AN - SCOPUS:85130495584

VL - 17

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e0268725

ER -

ID: 36544437