Genetic and Environmental Contributions to the Relationships Between Brain Structure and Average Lifetime Cigarette Use

Abstract

Chronic cigarette use has been consistently associated with differences in the neuroanatomy of smokers relative to nonsmokers in case-control studies. However, the etiology underlying the relationships between brain structure and cigarette use is unclear. A community-based sample of male twin pairs ages 51-59 (110 monozygotic pairs, 92 dizygotic pairs) was used to determine the extent to which there are common genetic and environmental influences between brain structure and average lifetime cigarette use. Brain structure was measured by high-resolution structural magnetic resonance imaging, from which subcortical volume and cortical volume, thickness and surface area were derived. Bivariate genetic models were fitted between these measures and average lifetime cigarette use measured as cigarette pack-years. Widespread, negative phenotypic correlations were detected between cigarette pack-years and several cortical as well as subcortical structures. Shared genetic and unique environmental factors contributed to the phenotypic correlations shared between cigarette pack-years and subcortical volume as well as cortical volume and surface area. Brain structures involved in many of the correlations were previously reported to play a role in specific aspects of networks of smoking-related behaviors. These results provide evidence for conducting future research on the etiology of smoking-related behaviors using measures of brain morphology.

Widespread associations between grey matter structure and the human phenome

“…Previous studies have reported association between tobacco usage and volume of left thalamus (Gallinat et al, 2006; Gillespie et al, 2018; Hanlon et al, 2016), which might be due to faster age related volume loss in smokers (Durazzo et al, 2017). We did not replicate other cortical or subcortical associations previously reported (Gallinat et al, 2006; Hanlon et al, 2016; Prom-Wormley et al, 2015). Alcohol intake was also associated with left thalamus thickness in the UKB, consistent with the significant grey-matter correlation ( Figure 2 ) between the two traits.…”

Efficient Genome-wide Association in Biobanks Using Topic Modeling Identifies Multiple Novel Disease Loci

“…In these analyses, only bi-allelic SNPs with minor allele frequencies of at least 1% were retained. Tests for association used linear regression assuming an additive allelic effect, treating each topic pulmonary disease, as well as multiple apparently novel disease loci for pregnancy complications, viral susceptibility, anemia/fracture risk and uterine cancer not previously associated at a genome-wide threshold with disease (based on searching the National Human Genome Research Institute-European Bioinformatics Institute Catalog of published genome-wide association studies) (25). We compared our results to those arising from a standard singlediagnostic-code PheWAS; this approach would not have yielded association at this threshold.…”

The genetic epidemiology of substance use disorder: A review

“…For example, small, widespread negative associations were recently reported between cigarette pack-years and the volume and/or surface area of several cortical as well as subcortical brain structures (Prom-Wormley et al, 2015). Importantly, correlations were the result of shared genetic and unique environmental factors in brain structures involved in the processing of environmental influences related to smoking.…”