The truth about complex traits and GWAS

This 2017 Colorado analysis, “No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes,” found:

“A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study [GWAS] conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance.

However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not.

As a group, variants in the most-studied candidate genes were no more associated with schizophrenia than were variants in control sets of noncandidate genes. While a small subset of candidate genes did appear to be significantly associated with schizophrenia, these genes were not particularly noteworthy given the large number of more strongly associated noncandidate genes.

The history of schizophrenia research should serve as a cautionary tale to candidate gene investigators examining other phenotypes: our findings indicate that the most investigated candidate gene hypotheses of schizophrenia are not well supported by genome-wide association studies, and it is likely that this will be the case for other complex traits as well.”

One reason I admire scientists is that many of them are genuinely interested in advancing science. They eventually expose the storytelling and directed narratives in reviews such as:

They uncover questionable methods and moneygrubbing to fund research with a goal of confirming sponsors’ biases such as:

They impartially examine evidence supporting agendas and personal aggrandizements in studies such as:

Unbiased facts and analyses are eventually reported by these dedicated scientists. The problem is that their works aren’t on page 1 of journals and search results. “No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes” (not freely available)


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