Workflow of <i>encG-reg</i> and its practical timeline as exercised in Chinese cohorts.

Abstract

The mathematical details of encG-reg are simply algebraic, but its inter-cohort implementation involves coordination. (A) We illustrate its key steps, the time cost of which was adapted from the present exercise for 9 Chinese datasets (here simplified as three cohorts). Cohort assembly: It took us about a week to call and got positive responses from our collaborators (See Table 3), who agreed with our research plan. Inter-cohort QC: we received allele frequencies reports from each cohort and started to implement inter-cohort QC according to “geo-geno” analysis (see Fig 6). This step took about two weeks. Encrypt genotypes: upon the choice of the exercise, it could be exhaustive design (see UKB example), which may maximize the statistical power but with increased logistics such as generating pairwise Sij; in the Chinese cohorts study we used parsimony design, and generated a unique S given 500 SNPs that were chosen from the 7,009 common SNPs. It took about a week to determine the number of SNPs and the dimension of k according to Eq 3 and 4, and to evaluate the effective number of markers. Perform encG-reg and validation: we conducted inter-cohort encG-reg and validated the results (see Fig 7 and Table 4). It took one week. (B) Two interactions between data owners and central analyst, including example data for exchange and possible attacks and corresponding preventative strategies.</p