African American Multiple Myeloma GWAS

The case set is from a case-control study designed to identify common genetic risk factors for multiple myeloma in African Americans, the population with the highest risk for this cancer. We conducted two GWAS and combined each of these with convenience controls consisting of unaffected African American participants in cohorts with existing GWAS data. We then conducted a meta-analysis of the two sets. Cases were persons of African ancestry with smoldering or active multiple myeloma identified at participating oncology clinics or through SEER registries, as part of the African American Multiple Myeloma Study (AAMMS) diagnosed from Jan 1, 1988 through July 31, 2016. The majority of the samples were collected from incident and prevalent cases diagnosed since Jan 1, 2008 (80.9%), with a minority obtained from biobanks from cases diagnosed prior to 2008 (19.1%). Additional samples were obtained from the Multiethnic Cohort (USC and University of Hawaii) (n=40), the University of California at San Francisco Multiple Myeloma Study (n=27), and from the Multiple Myeloma Research Consortium for secondary analysis (samples originally provided to MMRC by 8 additional sites (n=84)). We have identified the phenotype (smoldering myeloma, plasma cell multiple myeloma, or myeloma not otherwise specified (myeloma NOS) when myeloma phenotype was not known), sex and age at diagnosis in this data set. The initial GWAS set consisted of 1308 (1,305 passed QC) cases with DNA samples, with a GWAS performed on the Illumina Human Core. Controls consisted of 7,078 unaffected African American subjects who were participants in the African American Prostate and Breast Consortium, with existing GWAS data from the Illumina1M Duo BeadChip. The second GWAS set consisted of 529 African American multiple myeloma patients with samples (406 from University of Arkansas, results not contained in this dataset because NCI funds were not used for the collection and genotyping) with GWAS data resulting from the Illumina Mega-BeadChip v1.1. Controls were 2,390 unaffected African American participants in the Multiethnic Cohort with existing GWAS data from the same array. After QC and removal of duplicates within sets, sex mismatches, and removal of plasmacytoma cases (ICD-0 code 9731), this deposited data set contains the typed GWAS data for the Illumina Human Core (set 1) (n=1298), and for the MegaBead Chip v1.1 (set 2) (n=123), with the University of Arkansas samples removed, for a total of 1,421 case genotypes. Note that 13 samples that overlap set 1 and set 2 were included.]]> Inclusion criteria for patients ascertained by the 4 SEER registries were: 1)self-reported African ancestry (African American, Caribbean American, African) identified, 2) diagnosed multiple myeloma (ICD-O code 9732), 3) addresses could be traced, 4) alive at ascertainment, 5) from 20-85 years of age at diagnosis (for reliable telephone interview). Dates of diagnosis were Jan 1, 2010 through July 7, 2016 (all ended May 30, 2015 except Los Angeles). For retrospectively banked samples from cancer centers, patients diagnosed with smoldering myeloma or multiple myeloma with stored buffy coat, DNA or viably frozen cells, identified from hospital records as of African American, Caribbean American or African race. There was no limit on age at diagnosis or date of diagnosis. For incident or prevalent patients ascertained in cancer center clinics at diagnosis or consultation or during treatment or follow-up, criteria were patients diagnosed with smoldering myeloma or multiple myeloma self-identified as having African American, Caribbean American or African ancestry, at least 20 years of age, with no upper age limit. Recruitment began Jan 1, 2010 and ended May 30, 2015 for all but 3 centers. Enrollment of patients for this case set from these clinics ended November 30, 2016 (some ended earlier). Exclusion criteria: 1) allogenic bone marrow transplant within 6 months, 2) non-English speaking.]]> The study was a case only ascertainment of multiple myeloma patients of African descent with sample collection intended for a genome wide array scan. We planned the study as a case-control genome-wide association study using previously collected GWAS data from the AABC and AAPC cohorts as controls. Because myeloma is a relatively rare cancer and we were studying African Americans, we included a large umbrella of collaborators from cancer centers and SEER registries. There were several waves of genotyping on Illumina platforms Human Core and most recently, the MegaBead Chip, as samples were received, towards the end of the study. Two analyses have been conducted, one published in 2015 (Rand et al., CEBP) and the other is in preparation ( Du et al.)]]>