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PLINK 1 is a widely used open-source C/C++ toolset for genome-wideassociation studies (GWAS) and research in population genetics. However, thesteady accumulation of data from imputation and whole-genome sequencing studieshas exposed a strong need for even faster and more scalable implementations ofkey functions. In addition, GWAS and population-genetic data now frequentlycontain probabilistic calls, phase information, and/or multiallelic variants,none of which can be represented by PLINK 1's primary data format.  To address these issues, we are developing a second-generation codebase forPLINK. The first major release from this codebase, PLINK 1.9, introducesextensive use of bit-level parallelism, O(sqrt(n))-time/constant-spaceHardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmicimprovements. In combination, these changes accelerate most operations by 1-4orders of magnitude, and allow the program to handle datasets too large to fitin RAM. This will be followed by PLINK 2.0, which will introduce (a) a new dataformat capable of efficiently representing probabilities, phase, andmultiallelic variants, and (b) extensions of many functions to account for thenew types of information.  The second-generation versions of PLINK will offer dramatic improvements inperformance and compatibility. For the first time, users without access tohigh-end computing resources can perform several essential analyses of thefeature-rich and very large genetic datasets coming into use.

Second-generation PLINK: rising to the challenge of larger and richer datasets