Studies and Consortia

studies and consortia
Human genetic research in the 21st century is highly collaborative, and members of the Centers are among the leaders of these international efforts. Specifically, the center’s faculty are active members of several large studies and consortia that have been assembled to facilitate investigation into the genetic basis of disease. Many of these efforts are focused on multi-ethnic minority populations and lessening the health disparity experienced by these populations. Examples of such research include:

AAMMS was established in collaboration with 11 national cancer centers and four National Cancer Institute SEER registries to elucidate causes of multiple myeloma in African Americans, the highest risk group in the world. AAMMS has demographic, risk factor, detailed clinical phenotype and molecular data, serum, plasma, DNA and tissue samples from 1,810 African American multiple myeloma patients, the largest such collection in the world. GWAS has been conducted and genotypes are available, as well as imputed human leukocyte antigen types. Tumor tissue collection is ongoing.

Center members are leading GWAS, fine-mapping and polygenic risk score analyses of breast cancer among women of African Ancestry.

CTP is one of the largest population-based twin registries in the world, with 50,000 participating twins born in California from 1918 to 1982. The program is regularly linked to the California Cancer Registry and USC CSP to obtain cancer diagnoses (more than 1,420 twins with 1,596 breast cancers, 1,675 twins with prostate cancer and 1,320 twins with melanoma). Serum, DNA, environmental samples, mammographic density, immunologic measures and tumor blocks are available from subsets of twins.

CIRCLE is a National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency–funded program project focused on environmental risk factors for childhood leukemia and is a collaboration between USC, the University of California, Berkeley and Yale University. The Center for Genetic Epidemiology plays a major role in immunotoxicology, genetic and epigenetic projects within CIRCLE.

Click here for more information.

CCRLP involves linking several California-based databases to study all cancer types in children 0 to 19 years of age between 1988 and 2015 for which biological samples are available. CALSEC is a similar linkage covering cancer cases up to age 35 and up to the year 2015. These repositories form a basis for several cancer studies between USC, the University of California, Berkeley and Yale University.

The goal of the FinMetSeq consortium is to leverage the unique population bottleneck in Northern and Eastern Finland for increased power to map rare alleles (< 0.005%) associated with quantitative cardiometabolic traits. The consortium has generated more than 20,000 whole-exome sequences and is in the process of generating thousands of whole-genome sequences. This is a collaboration between Center for Genetic Epidemiology investigators and investigators at the Institute for Molecular Medicine Finland, McDonnell Genome Institute at Washington University in St. Louis, University of Michigan and University of California, Los Angeles.

IMAGE’s goal is to develop novel statistical methods to address some of the major problems facing cancer genetic epidemiologists in the post-GWAS era and to illustrate their use for discovery of novel biology in various colorectal cancer studies. These methods:

  • Leverage prior biological knowledge to inform integrative genomic analyses (project 1)
  • Use phylogenetic information to infer gene function as inputs to our epidemiologic modeling projects (project 2)
  • Model the role of the microbiome and the exposome in cancer risk (project 3)
  • Exploit intratumor heterogeneity to learn about somatic tumor evolution and how this process is modified by the internal environment (project 4)

These four projects are supported by an administrative core and three shared resource cores on functional annotation, high performance computing and software development and distribution. The entire program is motivated by an overall objective of providing tools for evaluating the impact of potential preventive or therapeutic interventions based on modifiable risk factors.

MEC is a large epidemiologic study that follows more than 215,000 residents of Hawaii and Los Angeles for development of cancer and other chronic diseases. It includes men and women of five main ethnic groups: Japanese Americans, Native Hawaiians, African Americans, Latinos and whites, with genome-wide association studies (GWAS) and biospecimens available for more than 70,000 individuals. More than 16,000 MEC individuals will also be whole-genome sequenced as part of the National Human Genome Research Institute’s Centers for Common Disease Genomics program.

Click here for more information.

PAGE includes genomics data from more than 120,000 diverse individuals from six well-characterized cohorts/biobanks. The goals of PAGE are to:

  • Identify genetic variants that influence complex traits and diseases in ancestrally diverse individuals using both whole-genome sequence data and GWAS data
  • Integrate information on sequence variation and “-omics” to better understand the genetic underpinnings of complex traits in the diverse PAGE participants
  • Characterize biological pathways underlying disease risk both within and between populations

Click here for more information.

As part of these consortia, center members are leading a number of GWAS and exome sequencing studies of prostate cancer and aggressive phenotypes across racial and ethnic populations in the U.S. and globally.

The RESPOND study is one of the largest studies ever to look at the underlying factors that put African American men at higher risk for prostate cancer. Over the next five years, 10,000 African American men with prostate cancer will be recruited.

Click here for more information.

The TOPMed program, which is supported by the National Heart, Lung, and Blood Institute, has collected whole-genome sequencing and other “-omics” data, including methylation, proteomics measurements, metabolites and RNA among diverse ethnic groups. Several broadly phenotyped epidemiologic studies contribute to the program, which integrates “-omics” data with molecular, behavioral, imaging, environmental and clinical data to improve the prevention and treatment of heart, lung, blood and sleep disorders. Center for Genetic Epidemiology faculty are currently actively involved in lung, hematology and inflammatory biomarkers working groups.

Click here for more information.

RTR is a tissue bank of donated formalin-fixed, paraffin-embedded tissue blocks from more than 75,000 patients diagnosed throughout Los Angeles County, a subset of the population covered by the SEER Cancer Registry for Los Angeles County (USC Cancer Surveillance Program [CSP]). Individual patient data, including demographics, clinical data and survival, is obtained by linkage to the USC CSP and the California Cancer Registry. RTR currently contains tumor blocks from more than 17,300 Hispanic, 10,900 African American, 7,600 Asian and 39,000 non-Hispanic white cancer patients.