Multi-omics cannot replace sample size in genome-wide association studies.

genetics GWAS human multi‐omics sample size transcriptomics National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027 R21AA027827 National Institute on Drug Abuse 10.13039/100000026 DA54750 K02DA32573 R01DA054750 R01DA054869 R33DA047527 T32DA007261 U01DA055367 For gene prioritization (i.e., genes that are proximal to GWAS significant loci in the smaller GWAS; Figure 2 ), genes that were identified both by proximity to a genome‐wide significant locus and by multi‐omics were more likely to be significant in the larger GWAS than genes only identified by a genome‐wide significant locus (Figure 2A ).

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This is particularly striking for positional methods, where prior expectations were high that “omics” might be helpful: most genes enriched for nominally significant loci did not contain a genome‐wide significant hit within the larger sample.

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