Cited by 28Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsGenetic and phenotypic traits in livestock

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

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Deming, Yuetiva, Xia, Jian, Cai, Yefei, Lord, Jenny, Del-Aguila, Jorge L., Fernandez, Maria Victoria, Carrell, David, Black, Kathleen +343 more·2016·Scientific Reports

Abstract

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects and complex disease associations in the same locus.

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Deming, Y., Xia, J., Cai, Y., Lord, J., Del-Aguila, J. L., Fernandez, M. V., Carrell, D., Black, K., Budde, J., Ma, S., Saef, B., Howells, B., Bertelsen, S., Bailey, M., Ridge, P. G., (ADNI), A. D. N. I., Hefti, F., Fillit, H., Zimmerman, E. A., Celmins, D., Brown, A. D., Carrillo, M., Fleisher, A., Reeder, S., Trncic, N., Burke, A., Tariot, P., Reiman, E. M., Chen, K., Sabbagh, M. N., Beiden, C. M., Jacobson, S. A., Sirrel, S. A., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Green, R. C., Marshall, G., Johnson, K. A., Sperling, R. A., Snyder, P., Salloway, S., Malloy, P., Correia, S., Bernick, C., Munic, D., Stern, Y., Honig, L. S., Bell, K. L., Relkin, N., Chaing, G., Ravdin, L., Paul, S., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Bates, V., Capote, H., Rainka, M., Friedl, K., Murali Doraiswamy, P., Petrella, J. R., Borges-Neto, S., James, O., Wong, T., Coleman, E., Schwartz, A., Cellar, J. S., Levey, A. L., Lah, J. J., Behan, K., Scott Turner, R., Johnson, K., Reynolds, B., Pearlson, G. D., Blank, K., Anderson, K., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Farlow, M. R., Saykin, A. J., Foroud, T. M., Shen, L., Faber, K., Kim, S., Nho, K., Marie Hake, A., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., Albert, M., Onyike, C., D’Agostino, D., Kielb, S., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Petersen, R., Jack, C. R., Bernstein, M., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Chertkow, H., Hosein, C., Mintzer, J., Spicer, K., Bachman, D., Grossman, H., Mitsis, E., Pomara, N., Hernando, R., Sarrael, A., Potter, W., Buckholtz, N., Hsiao, J., Kittur, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Johnson, N., Chuang-Kuo, Kerwin, D., Bonakdarpour, B., Weintraub, S., Grafman, J., Lipowski, K., Mesulam, M.-M., Scharre, D. W., Kataki, M., Adeli, A., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Borrie, M., Lee, T.-Y., Bartha, R., Martinez, W., Villena, T., Sadowsky, C., Khachaturian, Z., Ott, B. R., Querfurth, H., Tremont, G., Frank, R., Fleischman, D., Arfanakis, K., Shah, R. C., deToledo-Morrell, L., Sorensen, G., Finger, E., Pasternack, S., Rachinsky, I., Drost, D., Rogers, J., Kertesz, A., Furst, A. J., Chad, S., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Black, S., Stefanovic, B., Caldwell, C., Robin Hsiung, G.-Y., Mudge, B., Assaly, M., Fox, N., Schultz, S. K., Boles Ponto, L. L., Shim, H., Ekstam Smith, K., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Natelson Love, M., DeCarli, C., Carmichael, O., Olichney, J., Maillard, P., Fletcher, E., Nguyen, D., Preda, A., Potkin, S., Mulnard, R. A., Thai, G., McAdams-Ortiz, C., Landau, S., Jagust, W., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H. S., Lu, P. H., Bartzokis, G., Thompson, P., Donohue, M., Thomas, R. G., Walter, S., Gessert, D., Brewer, J., Vanderswag, H., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., Aisen, P., Davis, M., Morrison, R., Harvey, D., Thal, L., Beckett, L., Neylan, T., Finley, S., Weiner, M. W., Hayes, J., Rosen, H. J., Miller, B. L., Perry, D., Massoglia, D., Brawman-Mentzer, O., Schuff, N., Smith, C. D., Hardy, P., Sinha, P., Oates, E., Conrad, G., Koeppe, R. A., Lord, J. L., Heidebrink, J. L., Arnold, S. E., Karlawish, J. H., Wolk, D., Clark, C. M., Trojanowki, J. Q., Shaw, L. M., Lee, V., Korecka, M., Figurski, M., Toga, A. W., Crawford, K., Neu, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Womack, K., Mathews, D., Quiceno, M., Foster, N., Montine, T., Fruehling, J. J., Harding, S., Johnson, S., Asthana, S., Carlsson, C. M., Petrie, E. C., Peskind, E., Li, G., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Smith, A., Ashok Raj, B., Fargher, K., Kuller, L., Mathis, C., Ann Oakley, M., Lopez, O. L., Simpson, D. M., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Cairns, N. J., Raichle, M., Morris, J. C., Householder, E., Taylor-Reinwald, L., Holtzman, D., Ances, B., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Duara, R., Varon, D., Greig, M. T., Roberts, P., Varma, P., MacAvoy, M. G., Carson, R. E., van Dyck, C. H., Davies, P., Holtzman, D., Morris, J. C., Bales, K., Pickering, E. H., Lee, J.-M., Heitsch, L., Kauwe, J., Goate, A., Piccio, L., & Cruchaga, C.
Affiliations
  • Washington University in St. Louis (US)
  • Central South University (CN)
  • Brigham Young University (US)
  • Alzheimer's Drug Discovery Foundation (US)
  • Albany Medical College (US)
  • Alzheimer's Association (US)
  • Banner Alzheimer’s Institute (US)
  • Banner Sun Health Research Institute (US)
  • Baylor College of Medicine (US)
  • Boston University (US)
  • Brigham and Women's Hospital (US)
  • Brown University (US)
  • Butler Hospital (US)
  • Cleveland Clinic (US)
  • Columbia University Irving Medical Center (US)
  • Cornell University (US)
  • Dartmouth–Hitchcock Medical Center (US)
  • Dent Neurologic Institute (US)
  • United States Department of Defense (US)
  • Duke Medical Center (US)
  • Eli Lilly (United States) (US)
  • Emory University (US)
  • Georgetown University Medical Center (US)
  • Hartford Hospital (US)
  • Howard University (US)
  • Indiana University (US)
  • Johns Hopkins University (US)
  • Mayo Clinic in Florida (US)
  • Mayo Clinic (US)
  • McGill University (CA)
  • Medical University of South Carolina (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • National Institute on Aging (US)
  • New York University (US)
  • Northwestern University (US)
  • The Ohio State University (US)
  • Oregon Health & Science University (US)
  • Premiere Research Institute (US)
  • Rhode Island Hospital (US)
  • Rush University Medical Center (US)
  • Siemens (Germany) (DE)
  • St Joseph's Health Care (CA)
  • Stanford University (US)
  • Sunnybrook Health Science Centre (CA)
  • University College London (GB)
  • University of Iowa (US)
  • University of Kansas Medical Center (US)
  • University of Alabama at Birmingham (US)
  • University of California, Davis (US)
  • University of California, Irvine (US)
  • University of California, Berkeley (US)
  • University of California, Los Angeles (US)
  • University of California San Diego (US)
  • University of California, San Francisco (US)
  • University of Kentucky (US)
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  • University of Pennsylvania (US)
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  • The University of Texas Southwestern Medical Center (US)
  • University of Utah (US)
  • University of Washington (US)
  • University of Rochester Medicine (US)
  • University of South Florida (US)
  • University of Pittsburgh (US)
  • Wake Forest University (US)
  • Yale University (US)
  • Yeshiva University (US)
  • Pfizer (United States) (US)
Corresponding author
Cruchaga, Carlos
ORCID
Venue
Scientific Reports
Published
2016-01-04
Volume
6
Issue
1
Pages
18092-18092
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2225056762
Cited by
28
References
159
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 7 · 2017: 3 · 2016: 1
FWCI
3.50
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
  • Foundation for the National Institutes of Health (W81XWH-12-2-0012, U01AG024904, Grant U01 AG024904, AG024904)
  • National Multiple Sclerosis Society (JF 2144A2/1)
  • Alzheimer's Association (R01-AG044546, P01 AG003991, AG05681, U01 AG024904, NIRG-11-200110, W81XWH-12-2-0012)
  • American Federation for Aging Research
  • Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • Yale University
  • Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • University of Southern California (W81XWH-12-2-0012, P01 AG026276, U01 AG024904, P50 AG05681)
  • BrightFocus Foundation (A2013359S)
  • University of Pennsylvania
  • F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • Medpace (U01 AG024904)
  • Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Synarc (U01 AG024904)
  • Wake Forest University
  • Yeshiva University
  • Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, Department of Defense award number W81XWH-12-2-0012)
  • BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
  • University of Washington (P01 AG03991, P01 AG026276)
  • University of Pittsburgh
  • Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
  • Wellcome Trust (200110)
  • Hope Center for Neurological Disorders
  • Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • National Institutes of Health (5u01ag024904-10, W81XWH, NIH P50, W81XWH-12-2-0012, U01-AG024904, AG05681, Grant U01 AG024904, AG024904, AG003991, AG 03991, AG026276)
  • Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • University of California, Los Angeles
  • University of California, Davis
  • University of California, San Diego
  • University of California, San Francisco
  • University of California, Irvine
  • Medical Research Council (U01 AG024904, G0300429)
  • National Institute on Aging (U01-AG-024904, AG03991, W81XWH-12-2–0012, AG 024904, AG 05681, R01AG035083, U01AG032984, AG003991, P 50 AG05681, R01AG044546, AG026276, P50AG005681, P01 AG0 3991, P01AG003991, AG035083, P01AG026276)
  • National Institute of Neurological Disorders and Stroke (R01NS085419)
  • National Institute of Biomedical Imaging and Bioengineering (W81XWH-12-2-0012, U01 AG024904, AG024904)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords
plasma protein levels, biomarkers, complex traits, endophenotypes, pleiotropy, genome-wide association study, Turku, FUT2, apolipoprotein E, SELE, CA19-9, CEA, beta2-glycoprotein I, IL-6 receptor, LPA, C-reactive protein, heart disease, inflammatory bowel disease, type 2 diabetes, multiple sclerosis

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