Cannabis- and Substance-Related Epidemiological Patterns of Chromosomal Congenital Anomalies in Europe: Geospatiotemporal and Causal Inferential Study.

Abstract

Introduction: Laboratory data link cannabinoid exposure to chromosomal mis-segregation errors. Recent epidemiological reports confirm this link and raise concern that elevated chromosomal congenital anomaly rates (CCAR) may be occurring in Europe which is experiencing increased cannabis use, daily intensity of use and cannabinoid potency. Methods: CCAR data from Eurocat. Drug use data from the European Monitoring Centre for Drugs and Drug Addiction. Income from World Bank. Bivariate, multivariate, panel and geotemporospatial regressions analyzed. Inverse probability weighting of panel models and E-values used as major quantitative causal inferential methodologies. Results: In countries where daily cannabis use was rising the trend for CCA’s was upwards whereas in those where daily use was declining it was usually downwards (p = 0.0002). In inverse probability weighted panel models terms for cannabis metrics were significant for chromosomal disorders, trisomies 21 and 13 and Klinefelters syndrome from p < 2.2 × 10−16. In spatiotemporal models cannabis terms were positive and significant for chromosomal disorders, genetic disorders, trisomies 21, 18 and 13, Turners and Klinefelters syndromes from 4.28 × 10−6, 5.79 × 10−12, 1.26 × 10−11, 1.12 × 10−7, 7.52 × 10−9, 7.19 × 10−7 and 7.27 × 10−7. 83.7% of E-value estimates and 74.4% of minimum E-values (mEV) > 9 including four values each at infinity. Considering E-values: the sensitivity of the individual disorders was trisomy 13 > trisomy 21 > Klinefelters > chromosomal disorders > Turners > genetic syndromes > trisomy 18 with mEV’s 1.91 × 1025 to 59.31; and daily cannabis use was the most powerful covariate (median mEV = 1.91 × 1025). Conclusions: Data indicate that, consistent with reports from Hawaii, Canada, Colorado, Australia and USA, CCARs are causally and spatiotemporally related to metrics and intensity of cannabis exposure, directly impact 645 MB (21.5%) of the human genome and may implicate epigenomic-centrosomal mechanisms.