Chunk #30 — FROM GENE DISCOVERY TO POLYGENICITY: POLYGENIC AND WITHIN‐FAMILY APPROACHES TO ILLUMINATE MECHANISMS OF GENETIC RISK — Within‐family comparisons
Several studies document that the signals emerging from large‐scale genome‐wide association studies of complex behavioral outcomes are also associated with aspects of the environment that are correlated with the behavior under study, 135 leading to concerns about the degree to which downstream polygenic scores derived from these summary statistics may be confounded by the environment. For example, polygenic scores for schizophrenia and depression are associated with greater exposure to socioenvironmental risk factors (e.g., neighborhood crime and disorder, family poverty, residential mobility) across childhood and adolescence. 136 Establishing the unique and specific associations between polygenic risk and alcohol outcomes is particularly critical in view of the enthusiasm to incorporate polygenic scores as part of precision medicine efforts to identify and intervene with individuals who may be at risk. Sibling comparisons are uniquely powerful for clarifying the nature of associations observed in polygenic analyses. Biological full siblings reared together share the same home environment and a substantial portion of their genetic variation (50% on average), allowing for control of measured and unmeasured familial factors such as socioeconomic status, religious upbringing, urban–rural residency,
