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Once a single gene (or region) is implicated by a screen (linkage or association), it is necessary to examine it for potentially functional variations that might explain the linkage or association signal. For positional cloning efforts, this generally consisted of sequencing the minimum candidate region and identifying mutations that segregated with the trait in families. For complex traits, this effort is more difficult, and the variant being sought may be a more common, yet functional, polymorphism. Several strategies, including haplotype analysis, conditional analysis, and exhaustive sequencing, may be used in this case. The analyses required for such efforts are discussed in Chapters 8 and 9. However, statistical analysis of a single dataset only goes so far to establish a trait‐associated variant. Additional studies, including replication in independent datasets and functional studies in cellular and animal models, may be required to ultimately determine if a variant influences the biology underlying the complex trait.