| Application: | 42195, GWAS Meta-Analysis of T2D and Prostate Cancer |
| Title: | Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction |
| Size: | 1.8 MB |
| Archived: | 25 May 2021 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
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Notes
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.Application 42195
GWAS Meta-Analysis of T2D and Prostate Cancer
Type 2 Diabetes (T2D) and prostate cancer (PCa) are leading health problems both globally with differential risk across racial/ethnic groups. Genome-wide association studies (GWAS) have made important contributions towards understanding genetic susceptibility and biological mechanisms in T2D and PCa. However, there is growing recognition of the inadequate representation of diverse racial/ethnic populations in genetic studies, with concern regarding the translational impact of genetic findings on populations of non-European ancestry globally. Genetic data from ethnically diverse populations is crucial to powering genome-phenome association studies. Likewise, the lack of representation of diverse populations in genetic research will exacerbate global health disparities that exist for many diseases. PAGE (Population Architecture using Genomics and Epidemiology) was specifically developed to conduct genetic epidemiologic research in diverse populations particularly Hispanic/Latinos, African Americans, Asians, Native Hawaiians and Native Americans. Further, in collaboration with Illumina and others, PAGE has designed the Multi-Ethnic Genotyping Array (MEGA) which includes a GWAS scaffold to tag common and low frequency variants among global populations. Among 49,839 individuals of non-European ancestry from multiple cohorts and biobanks we are examining genetic risk factors that contribute to T2D disease risk via a multi-ethnic GWAS, fine mapping of significant regions, and meta-analysis with European populations. PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) is a growing consortium of 123 diverse study groups from Europe, Australia, Malaysia, China, Japan, India, Africa, Canada and the United States, committed to identifying variants that may be related to PCa risk. With the proposed research, we aim to compare ethnic specific findings to the European population of UK Biobank to understand why ethnic group disease rates differ by population for T2D and PCa, expand our current data to better understand the role of genetic contributions to T2D and PCa risk, and develop predictive tools for both diseases to inform clinical decisions across disparate populations.
| Lead investigator: | Dr Chris Haiman |
| Lead institution: | University of Southern California |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3443 | Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction | David V. Conti (+230) | 2021 | Nature Genetics |
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