With the growing evidence for the role of rare variants and copy number variation (CNV) in psychiatric disorders (18–20), linkage analysis remains a useful approach to gene discovery. An adequately powered linkage study can detect diverse kinds of genetic polymorphism that segregate in families, including common variants, multiple rare variants within one locus, and inherited CNVs. The apparent failure to identify association under linkage peaks could in part be attributable to the fact that often, only common variants are examined under the linkage peak, whereas the linkage signal could be caused by multiple rare variants with higher penetrance (21–23).
