Computational protocol: Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in African Americans

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Protocol publication

[…] We first performed a genome wide association study (GWAS) with >900,000 SNPs genotyped on the Illumina 1M Bead Chip. Assuming an additive genetic model, we performed single SNP tests of association in 736 T2D cases and 827 controls (n = 1,563) using logistic regression in PLINK . All tests were adjusted for age and sex.Using our GWAS genotype data we also performed an admixture scan on a subset of 4,333 autosomal ancestry informative markers (AIMs) on the Illumina 1M BeadChip . In this study we used ANCESTRYMAP to report global estimates of European ancestry for each individual and to identify disease loci throughout the genome. We tested AIMs for disease risk variants that differ in frequency across ancestral populations in this African American study population . We calculated ancestral allele frequency for all of the markers tested in two HapMap II reference populations, CEU and YRI. We also assumed a prior risk distribution of 1.2 (required for ANCESTRYMAP) with 100 burn in and 200 follow on iterations. Current admixture mapping software including ANCESTRYMAP does not allow for covariates in the model; therefore we were not able to adjust for age and sex, which might confound our analysis. ANCESTRYMAP uses two statistics to determine disease association: the genome-wide LOD score (LGS, >2.0 significant), the locus–specific LOD score (>5.0 significant, >4.0 suggestive), and the case-control statistic (CCS, >5.0, significant) .Pairwise LD (r2) was calculated and plotted using Haploview . Power calculations were performed using Quanto .For fine-mapping, we performed single SNP tests of association assuming an additive genetic model for SNPs with the TCIRG1 that passed QC in PLINK . Analyses were performed unadjusted and adjusted for age and sex. All results were plotted using Synthesis-View . To account for multiple testing, we employed Bonferroni correction and declared a significance threshold of p<0.001. LD was calculated by measuring the correlation coefficient r2 in Haploview . […]

Pipeline specifications

Software tools PLINK, ANCESTRYMAP, Haploview, Synthesis-View
Applications Population genetic analysis, GWAS
Diseases Diabetes Mellitus, Diabetes Mellitus, Type 2