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The more you test, the more you find: Smallest P-values become increasingly enriched with real findings as more tests are conducted

Increasing accessibility of data to researchers makes it possible to conduct massive amounts of statistical testing. Rather than follow a carefully crafted set of scientific hypotheses with statistical analysis, researchers can now test many possible relations and let P-values or other statistical summaries generate hypotheses for them. Genetic epidemiology field is an illustrative case in this paradigm shift. Driven by technological advances, testing a handful of genetic variants in relation to a health outcome has been abandoned in favor of agnostic screening of the entire genome, followed by selection of top hits, e.g., by selection of genetic variants with the smallest association P-values. At the same time, nearly total lack of replication of claimed associations that has been shaming the field turned to a flow of reports whose findings have been robustly replicating. Researchers may have adopted better statistical practices by learning from past failures, but we suggest that a steep increase in the amount of statistical testing itself is an important factor. Regardless of whether statistical significance has been reached, an increased number of tested hypotheses leads to enrichment of smallest P-values with genuine associations. In this study, we quantify how the expected proportion of genuine signals (EPGS) among top hits changes with an increasing number of tests. When the rate of occurrence of genuine signals does not decrease too sharply to zero as more tests are performed, the smallest P-values are increasingly more likely to represent genuine associations in studies with more tests.