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Chunk #2 — Introduction

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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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populations differ in their LD patterns, an index SNP discovered in one ancestral group (e.g. EA) may or may not be strongly correlated with the functional variant(s) in a different ancestral group (e.g. AA). Thus, the index SNP may not show evidence for replication in AAs; however, other SNPs in the region may be in high LD with the functional variant(s), and, hence, measuring these SNPs may further characterize associations within the genomic region. Therefore, a full exploration of potential replication/generalizability of GWAS findings in other ancestral groups requires investigating not only at the index SNP(s), but also examining, if possible, all variants of the region tagged by the index SNP(s). African populations are particularly suited for these studies because the LD pattern between SNPs tends to be substantially weaker than in other ancestral groups, as has been demonstrated for the FTO gene [30]. This process can reduce the number of potential functional variants for follow-up molecular investigation [33]. Given that functional studies can be labor- and cost-intensive, narrowing the associated region is an important step toward elucidating the underlying molecular mechanism. While molecular evaluation of the 16q12.2/FTO locus provides some promising leads [34], the putative functional variant(s) in this