the interpretability of associated loci. Although we have included diverse cohorts, our study lacked many major ancestral groups such as East Asians and South Asians. Furthermore, other forms of genetic variation, such as rare single variants69 or structural polymorphisms70 are likely to account for much of the “missing heritability” in genetic risk for TUD. Lastly, tobacco use can be greatly affected by environmental factors,12 such as cultural context, public health policies and characteristics related to socioeconomic status.71 Together with the existing body of literature,72–75 the strong genetic correlations between TUD and environmental influences, such as Townsend deprivation index, educational attainment and prenatal smoking, underscore the importance of considering environmental moderators in understanding the complex etiology of TUD. There is a great need in the field, therefore, to systematically assess sociocultural factors in healthcare settings.76
