Integrating plasma proteomes with genome-wide association data for causal protein identification in multiple myeloma

  • Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, Tuazon S, Gopal AK, Libby EN. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464–77.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Bladé J, Mateos MV, Rosiñol L, Boccadoro M, Cavo M, Lokhorst H, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011;118(17):4519–29.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shah N, Chari A, Scott E, Mezzi K, Usmani SZ. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. Leukemia. 2020;34(4):985–1005.

  • Cai X-W, Yu W-W, Yu W, Zhang Q, Feng W, Liu M-N, Sun M-H, Xiang J-Q, Zhang Y-W, Fu X-L. Tissue-based quantitative proteomics to screen and identify the potential biomarkers for early recurrence/metastasis of esophageal squamous cell carcinoma. Cancer Med. 2018;7(6):2504–17.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen Y, Quan L, Jia C, Guo Y, Wang X, Zhang Y, Jin Y, Liu A. Proteomics-based approach reveals the involvement of SERPINB9 in recurrent and relapsed multiple myeloma. J Proteome Res. 2021;20(5):2673–86.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ng YLD, Ramberger E, Bohl SR, Dolnik A, Steinebach C, Conrad T, Müller S, Popp O, Kull M, Haji M, et al. Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma. Nat Commun. 2022;13(1):1009.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–65.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Henry A, Gordillo-Marañón M, Finan C, Schmidt AF, Ferreira JP, Karra R, Sundström J, Lind L, Ärnlöv J, Zannad F, et al. Therapeutic targets for heart failure identified using proteomics and mendelian randomization. Circulation. 2022;145(16):1205–17.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shu X, Zhou Q, Sun X, Flesaker M, Guo X, Long J, Robson ME, Shu X-O, Zheng W, Bernstein JL. Associations between circulating proteins and risk of breast cancer by intrinsic subtypes: a Mendelian randomisation analysis. Br J Cancer. 2022;127(8):1507–14.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang Z, Yu R, Deng W, Wang W. Genetic evidence for the causal association between programmed death-ligand 1 and lung cancer. J Cancer Res Clin Oncol. 2021;147(11):3279–88.

    Article 
    PubMed 

    Google Scholar 

  • Considine DPC, Jia G, Shu X, Schildkraut JM, Pharoah PDP, Zheng W, Kar SP. Genetically predicted circulating protein biomarkers and ovarian cancer risk. Gynecol Oncol. 2021;160(2):506–13.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, Burgess S, Jiang T, Paige E, Surendran P, et al. Genomic atlas of the human plasma proteome. Nature. 2018;558(7708):73–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, Reeve MP, Laivuori H, Aavikko M, Kaunisto MA, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508–18.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.

    Article 
    PubMed 

    Google Scholar 

  • Finan C, Gaulton A, Kruger FA, Lumbers RT, Shah T, Engmann J, Galver L, Kelley R, Karlsson A, Santos R, et al. The druggable genome and support for target identification and validation in drug development. Sci Transl Med. 2017;9(383):eaag1166.

  • Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, et al. ChEMBL: towards direct deposition of bioassay data. Nucleic Acids Res. 2019;47(D1):D930–40.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gagliano Taliun SA, VandeHaar P, Boughton AP, Welch RP, Taliun D, Schmidt EM, Zhou W, Nielsen JB, Willer CJ, Lee S, et al. Exploring and visualizing large-scale genetic associations by using PheWeb. Nat Genet. 2020;52(6):550–2.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhou W, Zhao Z, Nielsen JB, Fritsche LG, LeFaive J, Gagliano Taliun SA, Bi W, Gabrielsen ME, Daly MJ, Neale BM, et al. Scalable generalized linear mixed model for region-based association tests in large biobanks and cohorts. Nat Genet. 2020;52(6):634–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.

    Article 
    PubMed 

    Google Scholar 

  • Liu M, Jiang Y, Wedow R, Li Y, Brazel DM, Chen F, Datta G, Davila-Velderrain J, McGuire D, Tian C, et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet. 2019;51(2):237–44.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, Alexander GE, Chen Z, Going SB. Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes (Lond). 2018;42(6):1161–76.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yengo L, Sidorenko J, Kemper KE, Zheng Z, Wood AR, Weedon MN, Frayling TM, Hirschhorn J, Yang J, Visscher PM, et al. Meta-analysis of genome-wide association studies for height and body mass index in 700000 individuals of European ancestry. Hum Mol Genet. 2018;27(20):3641–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smit RAJ, Trompet S, Dekkers OM, Jukema JW, le Cessie S. Survival bias in Mendelian randomization studies: a threat to causal inference. Epidemiology. 2019;30(6):813–6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang Q, Shi Q, Lu J, Wang Z, Hou J. Causal relationships between inflammatory factors and multiple myeloma: a bidirectional Mendelian randomization study. Int J Cancer. 2022;151(10):1750–9.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.

  • Brion M-JA, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies. Int J Epidemiol. 2013;42(5):1497–501.

    Article 
    PubMed 

    Google Scholar 

  • Machiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31(21):3555–7.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan N, Thompson J. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017;36(11):1783–802.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan NA, Thompson JR. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic. Int J Epidemiol. 2016;45(6):1961–74.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Bowden J, Smith GD, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhu Z, Zheng Z, Zhang F, Wu Y, Trzaskowski M, Maier R, Robinson MR, McGrath JJ, Visscher PM, Wray NR, et al. Causal associations between risk factors and common diseases inferred from GWAS summary data. Nat Commun. 2018;9(1):224.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet. 2017;13(11):e1007081.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zuber V, Colijn JM, Klaver C, Burgess S. Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization. Nat Commun. 2020;11(1):29.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zuber V, Gill D, Ala-Korpela M, Langenberg C, Butterworth A, Bottolo L, Burgess S. High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease. Int J Epidemiol. 2021;50(3):893–901.

    Article 
    PubMed 

    Google Scholar 

  • Julian TH, Cooper-Knock J, MacGregor S, Guo H, Aslam T, Sanderson E, Black GCM, Sergouniotis PI. Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration. Elife. 2023;12:e82546.

  • Kim G, Ouzounova M, Quraishi AA, Davis A, Tawakkol N, Clouthier SG, Malik F, Paulson AK, D’Angelo RC, Korkaya S, et al. SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model. Oncogene. 2015;34(6):671–80.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu Z-K, Li C, Zhang R-Y, Wei D, Shang Y-K, Yong Y-L, Kong L-M, Zheng N-S, Liu K, Lu M, et al. EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling. Mol Cancer. 2021;20(1):79.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cea M, Cagnetta A, Fulciniti M, Tai Y-T, Hideshima T, Chauhan D, Roccaro A, Sacco A, Calimeri T, Cottini F, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 2012;120(17):3519–29.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rickles RJ, Pierce LT, Giordano TP, Tam WF, McMillin DW, Delmore J, Laubach JP, Borisy AA, Richardson PG, Lee MS. Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies. Blood. 2010;116(4):593–602.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kumari R, Majumder MM, Lievonen J, Silvennoinen R, Anttila P, Nupponen NN, Lehmann F, Heckman CA. Prognostic significance of esterase gene expression in multiple myeloma. Br J Cancer. 2021;124(8):1428–36.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liang P, Cheng SH, Cheng CK, Lau KM, Lin SY, Chow EYD, Chan NPH, Ip RKL, Wong RSM, Ng MHL. Platelet factor 4 induces cell apoptosis by inhibition of STAT3 via up-regulation of SOCS3 expression in multiple myeloma. Haematologica. 2013;98(2):288–95.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhong Y, Meng F, Zhang W, Li B, van Hest JCM, Zhong Z. CD44-targeted vesicles encapsulating granzyme B as artificial killer cells for potent inhibition of human multiple myeloma in mice. J Control Release. 2020;320:421–30.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Raimondo S, Saieva L, Vicario E, Pucci M, Toscani D, Manno M, Raccosta S, Giuliani N, Alessandro R. Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesis. J Hematol Oncol. 2019;12(1):2.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fu J, Li S, Ma H, Yang J, Pagnotti GM, Brown LM, Weiss SJ, Mapara MY, Lentzsch S. The checkpoint inhibitor PD-1H/VISTA controls osteoclast-mediated multiple myeloma bone disease. Nat Commun. 2023;14(1):4271.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Westhrin M, Kovcic V, Zhang Z, Moen SH, Nedal TMV, Bondt A, Holst S, Misund K, Buene G, Sundan A, et al. Monoclonal immunoglobulins promote bone loss in multiple myeloma. Blood. 2020;136(23):2656–66.

    Article 
    PubMed 

    Google Scholar 

  • Terpos E, Zamagni E, Lentzsch S, Drake MT, García-Sanz R, Abildgaard N, Ntanasis-Stathopoulos I, Schjesvold F, de la Rubia J, Kyriakou C, et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e119–30.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hussain M, Khan F, Al Hadidi S. The use of bone-modifying agents in multiple myeloma. Blood Rev. 2023;57:100999.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mahony R, Ahmed S, Diskin C, Stevenson NJ. SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use? Cell Mol Life Sci. 2016;73(17):3323–36.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shao F, Pang X, Baeg GH. Targeting the JAK/STAT signaling pathway for breast cancer. Curr Med Chem. 2021;28(25):5137–51.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shanmugarajan S, Beeson CC, Reddy SV. Osteoclast inhibitory peptide-1 binding to the Fc gammaRIIB inhibits osteoclast differentiation. Endocrinology. 2010;151(9):4389–99.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee NK, Choi YG, Baik JY, Han SY, Jeong D-W, Bae YS, Kim N, Lee SY. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 2005;106(3):852–9.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Venkateshaiah SU, Khan S, Ling W, Bam R, Li X, van Rhee F, Usmani S, Barlogie B, Epstein J, Yaccoby S. NAMPT/PBEF1 enzymatic activity is indispensable for myeloma cell growth and osteoclast activity. Exp Hematol. 2013;41(6):547–557.e2.

  • Korotchkina L, Kazyulkin D, Komarov PG, Polinsky A, Andrianova EL, Joshi S, Gupta M, Vujcic S, Kononov E, Toshkov I, et al. OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis. Leukemia. 2020;34(7):1828–39.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang J-X, Chen Z-H, Chen D-L, Tian X-P, Wang C-Y, Zhou Z-W, Gao Y, Xu Y, Chen C, Zheng Z-S, et al. LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis. Oncogene. 2018;37(20):2660–75.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Paolillo R, Boulanger M, Gâtel P, Gabellier L, De Toledo M, Tempé D, Hallal R, Akl D, Moreaux J, Baik H, et al. The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias. Haematologica. 2022;107(11):2562–75.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Quach ND, Kaur SP, Eggert MW, Ingram L, Ghosh D, Sheth S, Nagy T, Dawson MR, Arnold RD, Cummings BS. Paradoxical role of glypican-1 in prostate cancer cell and tumor growth. Sci Rep. 2019;9(1):11478.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kaur SP, Verma A, Lee HK, Barnett LM, Somanath PR, Cummings BS. Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line. Sci Rep. 2021;11(1):9262.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • La Porta S, Roth L, Singhal M, Mogler C, Spegg C, Schieb B, Qu X, Adams RH, Baldwin HS, Savant S, et al. Endothelial Tie1-mediated angiogenesis and vascular abnormalization promote tumor progression and metastasis. J Clin Invest. 2018;128(2):834–45.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • D’Amico G, Korhonen EA, Anisimov A, Zarkada G, Holopainen T, Hägerling R, Kiefer F, Eklund L, Sormunen R, Elamaa H, et al. Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy. J Clin Invest. 2014;124(2):824–34.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cardinale A, Fusco FR. Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington’s disease. CNS Neurosci Ther. 2018;24(4):319–28.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mishra RR, Belder N, Ansari SA, Kayhan M, Bal H, Raza U, Ersan PG, Tokat ÜM, Eyüpoğlu E, Saatci Ö, et al. Reactivation of cAMP pathway by PDE4D inhibition represents a novel druggable axis for overcoming tamoxifen resistance in ER-positive breast cancer. Clin Cancer Res. 2018;24(8):1987–2001.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rahrmann EP, Collier LS, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, et al. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen. Cancer Res. 2009;69(10):4388–97.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ren H, Chen Y, Ao Z, Cheng Q, Yang X, Tao H, Zhao L, Shen A, Li P, Fu Q. PDE4D binds and interacts with YAP to cooperatively promote HCC progression. Cancer Lett. 2022;541:215749.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gupta DG, Varma N, Kumar A, Naseem S, Sachdeva MUS, Sreedharanunni S, Binota J, Bose P, Khadwal A, Malhotra P, et al. Genomic and proteomic characterization of Philadelphia-like B-lineage acute lymphoblastic leukemia: a report of Indian patients. Cancer. 2023;129(8):1217–26.

  • Chiou J, Su C-Y, Jan Y-H, Yang C-J, Huang M-S, Yu Y-L, Hsiao M. Decrease of FSTL1-BMP4-Smad signaling predicts poor prognosis in lung adenocarcinoma but not in squamous cell carcinoma. Sci Rep. 2017;7(1):9830.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang H, Che D, Gu Y, Cao D. Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma. Front Genet. 2022;13:940306.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gan J, Liu S, Zhang Y, He L, Bai L, Liao R, Zhao J, Guo M, Jiang W, Li J, et al. MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis. Exp Mol Med. 2022;54(8):1290–305.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Palmos AB, Millischer V, Menon DK, Nicholson TR, Taams LS, Michael B, Sunderland G, Griffiths MJ, Hübel C, Breen G. Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. PLoS Genet. 2022;18(3):e1010042.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Joshi H, Lin S, Fei KZ, Renteria AS, Jacobs H, Mazumdar M, Jagannath S, Bickell NA. Multiple myeloma, race, insurance and treatment. Cancer Epidemiol. 2021;73:101974.

  • Leave a Reply

    Your email address will not be published. Required fields are marked *