Lessons from Dwarf8 on the Strengths and Weaknesses of Structured Association Mapping

Abstract

The strengths of association mapping lie in its resolution and allelic richness, but spurious associations arising from historical relationships and selection patterns need to be accounted for in statistical analyses. Here we reanalyze one of the first generation structured association mapping studies of the Dwarf8 (d8) locus with flowering time in maize using the full range of new mapping populations, statistical approaches, and haplotype maps. Because this trait was highly correlated with population structure, we found that basic structured association methods overestimate phenotypic effects in the region, while mixed model approaches perform substantially better. Combined with analysis of the maize nested association mapping population (a multi-family crossing design), it is concluded that most, if not all, of the QTL effects at the general location of the d8 locus are from rare extended haplotypes that include other linked QTLs and that d8 is unlikely to be involved in controlling flowering time in maize. Previous independent studies have shown evidence for selection at the d8 locus. Based on the evidence of population bottleneck, selection patterns, and haplotype structure observed in the region, we suggest that multiple traits may be strongly correlated with population structure and that selection on these traits has influenced segregation patterns in the region. Overall, this study provides insight into how modern association and linkage mapping, combined with haplotype analysis, can produce results that are more robust.