We recommend applying PolyFun using in-sample LD from the GWAS target sample (i.e., using exactly the same samples in both the target and reference samples), assuming 10 causal SNPs per locus; we have facilitated this option for UK Biobank researchers by publicly releasing summary LD information for N=337K British-ancestry UK Biobank samples. As a second-best option we recommend applying PolyFun using LD-reference panel from the target sample population spanning at least 10% of the target sample size, while assuming 10 causal SNPs per locus. However, we caution that even subtle population differences may lead to false positive results. Hence, our published summary LD information files are unsuitable for analysis of summary statistics involving non-British UK Biobank individuals, or data from other cohorts or consortia44–46. However, researchers may use larger subsets of UK Biobank data to identify genome-wide significant loci, which they can fine-map using summary statistics and LD reference data based on N=337K British-ancestry individuals. In the absence of a reference panel from the target sample population spanning >10% of the target sample size, we recommend applying PolyFun without using an LD reference panel by restricting it to assume a single causal SNP per locus.
