The missing heritability of behavior: the search continues

Genetic variation altering behavior is elusive. This commentary discusses implications for the search for "missing heritability" posed by a unified series of studies from the Minnesota Center for Twin and Family Research. Endophenotypes are measured in a longitudinal cohort including twins, analyzed for heritability and genetically mapped via genome-wide association and genome sequencing. The genes identified account for a fraction of the heritability, but the manner in which the studies were conducted points to explanations other than methodology. The MCTFR data are an unprecedented addition to the research information commons. Other gene discoveries will follow when they are analyzed in new ways and in combination with other studies. Even larger samples may be needed. Alternatively or in addition, locus identification, especially rare alleles, may require the study of families and population isolates with founder characteristics.