Continuous Inflation Analysis: A Threshold-Free Method to Estimate Genetic Overlap and Boost Power in Imaging Genetics. A Threshold-Free Method to Estimate Genetic Overlap and Boost Power in Imaging Genetics.

Methods to quantify genetic overlap may elucidate relationships between disparate traits and provide Bayesian priors to guide the search for genetic influences on brain measures. Here we describe a threshold-free method called continuous inflation analysis, which we used to compare genome-wide association statistics (GWAS) for the volumes of eight brain regions, computed from brain magnetic resonance imaging. Our goal was to understand the extent of pleiotropy (overlap in genetic influences) and concordance for the volumes of brain regions with different biological functions. We found significant pleiotropy among seven of the subcortical brain volumes. We found positive concordance across the seven subcortical structures and negative concordance between genetic influences on each subcortical structure and intracranial volume. Using a conditional false discovery rate approach, we showed that a given brain volume GWAS could act as a Bayesian prior and improve the power to detect novel associations in a related brain volume. When conditioning the putamen volume GWAS on the caudate volume GWAS, we identified 17 novel loci associated with putamen volume.