ArticleResearch square2025
Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.
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Authors and funding
52 authors.
Jayna C NicholasDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Daniel H KatzCardiovascular Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0001-7237-8502
Usman A TahirDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID 0000-0002-3657-6082
Catherine L DebbanDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
Francois AguetBroad Institute, Cambridge, MA, USA.
Thomas BlackwellUniversity of Michigan, Ann Arbor, MI, USA.
Russell P BowlerNational Jewish Health, National Jewish Health, Denver, CO, USA.ORCID 0000-0003-4651-363X
K Alaine BroadawayDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jingsha ChenJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Clary B ClishMetabolomics Platform, Broad Institute, Cambridge, MA, USA.ORCID 0000-0001-8259-9245
Josef CoreshDepartment of Population Health, Institute for Optimal Aging, New York, NY, USA.ORCID 0000-0002-4598-0669
Elaine CornellLarner College of Medicine at the University of Vermont, Burlington, VT, USA.
Daniel E CruzDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Rajat DeoDivision of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Margaret F DoyleDepartment of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA.
Peter DurdaDepartment of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA.
Lynette EkunweUniversity of Mississippi Medical Center, Jackson, MS, USA.
James S FloydSchool of Medicine, University of Washington, Seattle, WA, USA.
Dipender GillSequoia Genetics, London, London, UK.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0002-5264-5068
Ron C HoogeveenMedicine, Cardiovascular Research, Baylor College of Medicine, Houston, TX, USA.
Craig JohnsonUniversity of Washington, Seattle, WA, USA.ORCID 0000-0002-3161-3753
Leslie A LangeSchool of Medicine, Colorado Anschutz Medical Campus, Aurora, CO, USA.
Yun LiDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-9275-4189
Alisa ManningBroad Institute, Harvard University, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-0247-902X
James B MeigsDepartment of Medicine, Division of General Internal Medicine, Broad Institute, Boston, MA, USA.
Michael Y MiDepartment of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Josyf C MychaleckyjDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-2595-0005
Nels C OlsonDepartment of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA.
Katherine A PratteDepartment of Biostatistics, National Jewish Health, Denver, CO, USA.
Brucy M PsatyCardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7278-2190
Alexander P ReinerFred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.ORCID 0000-0002-1427-4470
Peifeng RuanUT Southwestern, Dallas, TX, USA.ORCID 0000-0002-1364-7992
Magdalena Sevilla-GonzalezClinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA.
Amil M ShahHarvard Medical School, Boston, MA, USA.ORCID 0000-0003-1056-4451
Quan SunDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-8324-2803
Russell P TracyDepartment of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA.
Jia WenDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-3273-7704
Alexis C WoodUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0001-7616-2119
James G WilsonDeparment of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Kristin L YoungDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-0070-6145
Bing YuUT Health, School of Public Health, Houston, TX, USA.ORCID 0000-0003-4818-1077
Mary R RooneyDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0002-5607-4848
Ani ManichaikulDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0002-5998-795X
Ruth DubinUT Southwestern, Dallas, TX, USA.ORCID 0000-0002-0498-1980
Karen L MohlkeDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-6721-153X
Stephen S RichDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-3872-7793
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0001-7191-1723
Peter GanzDivision of Cardiology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0437-8882
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID 0000-0002-6767-7687
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-7892-193X
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MNHLBI Data Stage Coordinating CenterOT3HL147154 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ashok Kumar Krishnamurthy · 2018 to 2026
$98.9MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MBiostatstics for Research in Environmental HealthT32ES007018 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel, Rebecca Fry · 1985 to 2026
$31.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MThe Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142481 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI GROSSMAN, ROBERT L., PATEN, BENEDICT · 2017 to 2020
$24.9MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MUCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5MThe Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142478 · NHLBI · SEVEN BRIDGES GENOMICS, INC. · PI DAVIS-DUSENBERY, BRANDI NICOLE · 2017 to 2022
$12.6MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR033176NHGRI NIH HHS U54 HG003067NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS OT3 HL142478NHLBI NIH HHS OT3 HL142479NHLBI NIH HHS OT3 HL142480NHLBI NIH HHS OT3 HL142481NHLBI NIH HHS OT3 HL147154NHLBI NIH HHS R01 HL071051NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL071250NHLBI NIH HHS R01 HL071251NHLBI NIH HHS R01 HL071258NHLBI NIH HHS R01 HL071259NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL133870NHLBI NIH HHS R01 HL146860NHLBI NIH HHS R01 HL151855NHLBI NIH HHS R01 HL159081NHLBI NIH HHS U01 HL120393NIA NIH HHS U01 AG082042NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK072193NIDDK NIH HHS UM1 DK078616NIEHS NIH HHS T32 ES007018NIGMS NIH HHS T32 GM135128
Abstract
Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.30). Protein measures from each platform were associated with genetic variants (pQTLs), and one-third of the pQTL signals were driven by protein-altering variants (PAVs). We highlight 80 proteins that correlate differently across ancestry groups likely due to differing PAV frequencies by ancestry. Furthermore, adjustment for PAVs with opposite directions of effect by platform improved inter-platform protein measure correlation and resulted in more concordant genetic and phenotypic associations. Hence, PAVs need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.
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