Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of the genotype calls made by the commonly used platforms. Here we use replicate high-coverage sequencing of blood and saliva DNA samples from four European-American individuals to estimate lower bounds on the error rates of Complete Genomics and Illumina HiSeq whole-genome and whole-exome sequencing. Error rates for nonreference genotype calls range from 0.1% to 0.6%, depending on the platform and the depth of coverage. Additionally, we found (1) no difference in the error profiles or rates between blood and saliva samples; (2) Complete Genomics sequences had substantially higher error rates than Illumina sequences had; (3) error rates were higher (up to 6%) for rare or unique variants; (4) error rates generally declined with genotype quality (GQ) score, but in a nonlinear fashion for the Illumina data, likely due to loss of specificity of GQ scores greater than 60; and (5) error rates increased with increasing depth of coverage for the Illumina data. These findings, especially (3)- (5), suggest that caution should be taken in interpreting the results of next-generation sequencing-based association studies, and even more so in clinical application of this technology in the absence of validation by other more robust sequencing or genotyping methods.

Objectives We examined the pattern of the passage of smoking laws across venues (government and private workplaces, restaurants, bars) and by strength (no law to 100% smoke-free). Methods We conducted transition analyses of local and state smoking restrictions passed between 1970 and 2009, with data from the Americans for Nonsmokers' Rights Ordinance Database. Results Each decade, more laws were enacted, from 18 passed in the 1970s to 3172 in the first decade of this century, when 91% of existing state laws were passed. Most laws passed took states and localities from no law to some level of smoking restriction, and most new local (77%; 5148/6648) and state (73%; 115/158) laws passed in the study period did not change strength. Conclusions Because these laws are “sticky”—once a law has passed, strength of the law and venues covered do not change often—policymakers and advocates should focus on passing strong laws the first time, rather than settling for less comprehensive laws with the hope of improving them in the future.