False positives in imaging genetics

NeuroImage
Andreas Meyer-LindenbergDaniel R Weinberger

Abstract

Imaging genetics provides an enormous amount of functional-structural data on gene effects in living brain, but the sheer quantity of potential phenotypes raises concerns about false discovery. Here, we provide the first empirical results on false positive rates in imaging genetics. We analyzed 720 frequent coding SNPs without significant association with schizophrenia and a subset of 492 of these without association with cognitive function. Effects on brain structure (using voxel-based morphometry, VBM) and brain function, using two archival imaging tasks, the n-back working memory task and an emotional face matching task, were studied in whole brain and regions of interest and corrected for multiple comparisons using standard neuroimaging procedures. Since these variants are unlikely to impact relevant brain function, positives obtained provide an upper empirical estimate of the false positive association rate. In a separate analysis, we randomly permuted genotype labels across subjects, removing any true genotype-phenotype association in the data, to derive a lower empirical estimate. At a set correction level of 0.05, in each region of interest and data set used, the rate of positive findings was well below 5% (0.2-4.1%). T...Continue Reading

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Citations

Jan 7, 2009·Archives of General Psychiatry·Eric FakraAhmad R Hariri
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