{"doi":"10.1016/j.bpsgos.2023.09.006","title":"Investigating the Relationship Between Smoking Behavior and Global Brain Volume","abstract":"Previous studies have shown that brain volume is negatively associated with cigarette smoking, but there is an ongoing debate whether smoking causes lowered brain volume or a lower brain volume is a risk factor for smoking. We address this debate through multiple methods that evaluate directionality: Bradford Hill’s Criteria that is commonly used to understand a causal relationship in epidemiological studies, and mediation analysis. In 32,094 participants of European descent from the UK Biobank dataset, we examined the relationship between a history of daily smoking and brain volumes, as well as association of genetic risk score to ever smoking with brain volume. A history of daily smoking is strongly associated with decreased brain volume, and a history of heavier smoking is associated with a greater decrease in brain volume. The strongest association was between total grey matter volume and a history of daily smoking (Effect size = -2964mm3 p-value = 2.04 x 10-16), and there was a dose response relationship with more pack years smoked associated with a greater decrease in brain volume. A polygenic risk score (PRS) for smoking initiation was strongly associated with a history of daily smoking (Effect size = 0.05, p-value = 4.20 ×10-84), yet only modestly associated with total grey matter volume (Effect size = - 424mm3, p-value = 0.01). Mediation analysis indicated that a history of daily smoking is a mediator between smoking initiation PRS and total grey matter volume. A history of daily smoking is strongly associated with a decreased total brain volume.","journal":"Biological Psychiatry Global Open Science","year":2023,"id":335646,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1065557,"name":"Vera Thornton","orcid":"0000-0003-4090-4744","position":1,"is_corresponding":false},{"id":1065558,"name":"Ariya Chaloemtoem","orcid":"0000-0003-0188-2431","position":2,"is_corresponding":false},{"id":320085,"name":"Andrey P. Anokhin","orcid":"0000-0001-8158-6346","position":3,"is_corresponding":false},{"id":458425,"name":"Janine Bijsterbosch","orcid":"0000-0002-1385-9178","position":4,"is_corresponding":false},{"id":232788,"name":"Ryan Bogdan","orcid":"0000-0002-1430-1045","position":5,"is_corresponding":false},{"id":230708,"name":"Dana B. Hancock","orcid":"0000-0003-2240-3604","position":6,"is_corresponding":false},{"id":14691,"name":"Eric O. Johnson","orcid":"0000-0002-8870-1949","position":7,"is_corresponding":false},{"id":14720,"name":"Laura J. Bierut","orcid":"0000-0002-9952-4810","position":8,"is_corresponding":false},{"id":916644,"name":"Yoonhoo Chang","orcid":"0000-0002-6215-8466","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:10:02.777338Z","pmid":"38130847","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}