Whole exome sequencing was performed at the Broad Institute of MIT and Harvard (Cambridge, MA, USA) in a subset of 6,552 UK Biobank participants. Libraries were constructed as previously reported (Fisher et al., 2011) and sequenced on an Illumina HiSeq sequencer with the use of 151 bp paired-end reads. In-solution hybrid selection was performed using the Illumina Nextera Exome Kit. Aligned non-duplicate reads were locally realigned and base qualities were recalibrated using Genome Analysis Toolkit software (McKenna et al., 2010; Van der Auwera et al., 2013). Variants were jointly called using Genome Analysis Toolkit HaplotypeCaller software. We removed samples with contamination > 10% (N = 0), samples with < 80% of target bases at 20X coverage (N = 3), samples with discordance between self-reported and genetic sex (N = 0), and samples with discordant reported versus genotypic sex (N = 2). Mean target coverage among the remaining 6,547 samples was 75X, and 91.4% of target bases were captured at >20X sequencing depth. The subset of rare (allele frequency < 1%) variants in the melanocortin 4 receptor gene (MC4R; Ensemble transcript
