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Chunk #36 — Materials and Methods — Imputation to 1000 Genomes Project

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A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.
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To impute to the 1000 Genomes Project we used as the reference panel the haplotypes of the 1092 samples (all populations) from release version 2 of the 1000 Genomes Project Phase I (ftp://ftp-trace.ncbi.nih.gov/1000genomes/ftp/release/20110521) [52]. Combining reference data from all populations has been found to improve imputation accuracy of the low-frequency variants [53], and, hence, is recommended. We built the target panel by combining all genotype data in the FTO region from all studies. We used genotyped data from the Metabochip for all studies, except for WHI SNP Health Association Resource (SHARe, n = 6,326 samples) where we used genotype data from the Affymetrix 6.0 platform. The target panel was phased using Beagle [54]. We then performed a haplotype-to-haplotype imputation to estimate genotypes (as allele dosages) at 1000 Genomes Project variants. The phased target panel was imputed to the interval 53.5–54.2 Mb on chromosome 16 of the 1000 genomes reference panel using minimac [55]. To evaluate the quality of each imputed SNP we calculated Rsq. We excluded imputed SNPs with Rsq<0.9 for SNPs with allele frequency <0.5%, Rsq<0.8 for SNPs with