Hierarchical Bayesian methods enable information sharing across regression problems on multiple groups of data. While standard practice is to model regression parameters (effects) as (1) exchangeable across the groups and (2) correlated to differing degrees across covariates, we show that this approach exhibits poor statistical performance when the number of covariates exceeds the number of groups. For instance, in statistical genetics, we might regress dozens of traits (defining groups) for thousands of individuals (responses) on up to millions of genetic variants (covariates). When an analyst has more covariates than groups, we argue that it is often preferable to instead model effects as (1) exchangeable across covariates and (2) correlated to differing degrees across groups. To this end, we propose a hierarchical model expressing our alternative perspective. We devise an empirical Bayes estimator for learning the degree of correlation between groups. We develop theory that demonstrates that our method outperforms the classic approach when the number of covariates dominates the number of groups, and corroborate this result empirically on several high-dimensional multiple regression and classification problems.

MOTIVATION: LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously. RESULTS: In this manuscript, we describe LD Hub - a centralized database of summary-level GWAS results for 173 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies. AVAILABILITY AND IMPLEMENTATION: The web interface and instructions for using LD Hub are available at http://ldsc.broadinstitute.org/ CONTACT: [email protected] information: Supplementary data are available at Bioinformatics online.

Given a high-dimensional data set, we often wish to find the strongest relationships within it. A common strategy is to evaluate a measure of dependence on every variable pair and retain the highest-scoring pairs for follow-up. This strategy works well if the statistic used (a) has good power to detect non-trivial relationships, and (b) is equitable, meaning that for some measure of noise it assigns similar scores to equally noisy relationships regardless of relationship type (e.g., linear, exponential, periodic). In this paper, we define and theoretically characterize two new statistics that together yield an efficient approach for obtaining both power and equitability. To do this, we first introduce a new population measure of dependence and show three equivalent ways that it can be viewed, including as a canonical smoothing of mutual information. We then introduce an efficiently computable consistent estimator of our population measure of dependence, and we empirically establish its equitability on a large class of noisy functional relationships. This new statistic has better bias/variance properties and better runtime complexity than a previous heuristic approach. Next, we derive a second, related statistic whose computation is a trivial side-product of our algorithm and whose goal is powerful independence testing rather than equitability. We prove that this statistic yields a consistent independence test and show in simulations that the test has good power against independence. Taken together, our results suggest that these two statistics are a valuable pair of tools for exploratory data analysis.

Floating codes are codes designed to store multiple values in a Write Asymmetric Memory, with applications to flash memory. In this model, a memory consists of a block ofncells, with each cell in one of q states {0,1,...,q -1}. The cells are used to represent k variable values from an ¿-ary alphabet. Cells can move from lower values to higher values easily, but moving any cell from a higher value to a lower value requires first resetting the entire block to an all 0 state. Reset operations are to be avoided; generally a block can only experience a large but finite number of resets before wearing out entirely. A code here corresponds to a mapping from cell states to variable values, and a transition function that gives how to rewrite cell states when a variable is changed. Previous work has focused on developing codes that maximize the worst-case number of variable changes, or equivalently cell rewrites, that can be experienced before resetting. In this paper, we introduce the problem of maximizing theexpectednumber of variable changes before resetting, given an underlying Markov chain that models variable changes. We demonstrate that codes designed for expected performance can differ substantially from optimal worst-case codes, and suggest constructions for some simple cases. We then study the related question of the performance of random codes, again focusing on the issue of expected behavior.