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). Conclusion: 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.

Socioeconomic, Ethnocultural, Substance- and Cannabinoid-Related Epidemiology of Down Syndrome USA 1986–2016: Combined Geotemporospatial and Causal Inference Investigation

“…The strength of evidence provided in this paper is stronger than that reported previously from other independent datasets and jurisdictions. The present results are reminiscent of recent powerful studies in Europe on this issue [ 14 , 15 , 18 ].…”

“…A similar link was recently shown in Colorado where Down syndrome has risen over the decade of cannabis legalization and where the rise is associated more with increased cannabis use during a period where rates of tobacco and alcohol consumption were declining [ 11 , 12 ]. Similar findings also emerge from an Australian report [ 13 ] and recent European reports [ 14 , 15 , 16 ]. Interestingly congenital heart disease has also increased in line with cannabis consumption in Hawaii, Canada, Colorado and Europe [ 6 , 8 , 12 , 14 , 15 , 17 , 18 , 19 ].…”

“…Similar findings also emerge from an Australian report [ 13 ] and recent European reports [ 14 , 15 , 16 ]. Interestingly congenital heart disease has also increased in line with cannabis consumption in Hawaii, Canada, Colorado and Europe [ 6 , 8 , 12 , 14 , 15 , 17 , 18 , 19 ]. However, the important issue of the relationship of cannabis use with Down syndrome in the rich databases of the USA more generally has not as yet been considered in detail but has only been mentioned en passant [ 20 ].…”

“…Recent reports have found strong bivariate relationships between exposure to cannabis and many cannabinoids and both the raw Down syndrome rate (DSR) and estimates of the DSR corrected for early termination of pregnancy for anomaly (ETOPFA) across USA [ 17 ]. Similar recent powerful reports have issued from Europe [ 14 , 15 ]. However, this link has not been studied in a formal space-time relationship within a causal inferential framework in USA.…”

“…Importantly a longitudinal study of the effects of cannabis on the human and rodent epigenome by DNA methylation noted many changes in the machinery of the centromere and kinetochore and damage to the polymerized tubulin polymers of the microtubules of the mitotic spindle induced by cannabis dependence and withdrawal which will greatly increase the error rate of chromosomal segregation, and lead to chromosomal isolation independent of the mitotic spindle, aneuploidy and micronucleus formation [ 63 ]. These changes are discussed at length elsewhere [ 9 , 15 , 66 , 67 ].…”