Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings

Uptake of Genetic Testing Among Patients with Cancer At Risk for Lynch Syndrome in the National Health Interview Survey.

Lynch syndrome is the most common inherited cancer syndrome that increases the risk of developing colorectal and endometrial cancer. Universal screening guidelines were first recommended by the Centers for Disease Control and Prevention (CDC) in 2009 and are updated annually by multiple societies. Therefore, one would expect genetic testing rates to increase over time. But testing remains underutilized among those with colorectal or endometrial cancer, even though early detection can improve prognosis and survival rates. In this study, we aimed to understand differences in genetic testing uptake among those with colorectal cancer or endometrial cancer from 2005, 2010, 2015, using data from the National Health Interview Survey (NHIS). We examined genetic testing uptake across cancer-type, age (≤50 or ≥51), sex, race, insurance, and education using a χ2 statistical analysis. Despite an upward genetic testing trend in 2010, we found no significant differences in genetic testing uptake over time. In 2010, non-White individuals experienced the highest increase from 2005 in comparison with White individuals. However, genetic testing rates declined for both groups by 2015. Our findings show that genetic testing for colorectal cancer and endometrial cancer did not increase over a 10-year period in spite of guidelines that recommend testing.Prevention Relevance: Genetic testing uptake for colorectal cancer and endometrial cancer has not increased over a 10-year period in spite of universal screening guidelines. More genetic testing education is needed at the provider and patient level to improve screening strategies for cancer patients who are most at risk for Lynch syndrome