SNP-based estimates account for considerably more—21–45% of the twin-estimated heritable variance—there remains a majority of that heritable variance to be explained. There is much conjecture about the source of remaining additive genetic variance, including non-additive or rare SNP effects, additive and non-additive structural variation (e.g., CNVs, insertions/deletions), gene-environment interaction, or gene-gene interaction (Manolio et al., 2009; Zuk, Hechter, Sunyaev, & Lander, 2012). Further research involving much larger samples and more comprehensive genotyping, such as whole genome sequencing or rare variant chips, will be necessary to tackle these issues.
