Challenges and directions: an analysis of Genetic Analysis Workshop 17 data by collapsing rare variants within family data

摘要

Recent studies suggest that the traditional case-control study design does not have sufficient power to discover rare risk variants. Two different methods—collapsing and family data—are suggested as alternatives for discovering these rare variants. Compared with common variants, rare variants have unique characteristics. In this paper, we assess the distribution of rare variants in family data. We notice that a large number of rare variants exist only in one or two families and that the association result is largely shaped by those families. Therefore we explore the possibility of integrating both the collapsing method and the family data method. This combinational approach offers a potential power boost for certain causal genes, including VEGFA , VEGFC , SIRT1 , SREBF1 , PIK3R3 , VLDLR , PLAT , and FLT4 , and thus deserves further investigation.