{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:48:52Z","timestamp":1791582532953,"version":"4.3.4"},"reference-count":68,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567\/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE]\u00a0\u00b10.04) and 15% (SE\u00a0\u00b10.11) for MM and MGUS risk, respectively, and a 55% (SE\u00a0\u00b10.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020001435","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T15:39:38Z","timestamp":1592840378000},"page":"2789-2797","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":26,"title":["Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance"],"prefix":"10.1182","volume":"4","author":[{"given":"Alyssa I.","family":"Clay-Gilmour","sequence":"first","affiliation":[{"name":"Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN;"},{"name":"Department of Biostatistics and Epidemiology, Arnold School of Public Health, University of South Carolina, Greenville, SC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A. T.","family":"Hildebrandt","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine at the; University of Alabama, Birmingham, AL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1043-5812","authenticated-orcid":false,"given":"Jonathan N.","family":"Hofmann","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institues of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9119-3287","authenticated-orcid":false,"given":"John J.","family":"Spinelli","sequence":"first","affiliation":[{"name":"Division of Population Oncology, BC Cancer, BC, Canada;"},{"name":"School of Population and Public Health, University of British Columbia, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-9099","authenticated-orcid":false,"given":"Graham G.","family":"Giles","sequence":"first","affiliation":[{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia;"},{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia;"},{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Cozen","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, Keck School of Medicine at University of Southern California, Los Angeles, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parveen","family":"Bhatti","sequence":"first","affiliation":[{"name":"Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA;"},{"name":"Cancer Control Research, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie G.","family":"Waller","sequence":"first","affiliation":[{"name":"Division of Hematology and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alem A.","family":"Belachew","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis P.","family":"Robinson","sequence":"first","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Norman","sequence":"first","affiliation":[{"name":"Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN;"},{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1964-5522","authenticated-orcid":false,"given":"Jason P.","family":"Sinnwell","sequence":"first","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja I.","family":"Berndt","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institues of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-1833","authenticated-orcid":false,"given":"S. Vincent","family":"Rajkumar","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-9284","authenticated-orcid":false,"given":"Shaji K.","family":"Kumar","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Chanock","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institues of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell J.","family":"Machiela","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institues of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-7268","authenticated-orcid":false,"given":"Roger L.","family":"Milne","sequence":"first","affiliation":[{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia;"},{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia;"},{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Slager","sequence":"first","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Camp","sequence":"first","affiliation":[{"name":"Division of Hematology and Huntsman Cancer Institute, 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