Implications of family history and polygenic risk scores for causation

To the Editor: Mars and colleagues1 investigated the risk associations of having a family history, and of a genome-wide polygenic risk score (PRS), for 24 common diseases using the extraordinary FinnGen resource. They first estimated the marginal associations and then the conditional associations by fitting both family history and PRS together. Creatively, they did this separately for family history defined by first- and by second-degree relatives, and the results differed. We believe that their analyses have important implications for understanding both the causes of familial aggregation and the causes of the diseases themselves, specifically: (1) there is evidence for non-genetic causes of familial aggregation, (2) the PRS appears to capture a substantial causal effect, and (3) some of the non-genetic familial causes are confounded with the PRS.

Source: The American Journal of Human Genetics - July 6, 2023 Category: Genetics & Stem Cells Authors: Shuai Li, John L. Hopper Tags: Letter to the editor Source Type: research