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Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

ABSTRACT: Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (n_combined = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD.

SUBMITTER: Toikumo S

PROVIDER: S-EPMC11199106 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Toikumo Sylvanus S Jennings Mariela V MV Pham Benjamin K BK Lee Hyunjoon H Mallard Travis T TT Bianchi Sevim B SB Meredith John J JJ Vilar-Ribó Laura L Xu Heng H Hatoum Alexander S AS Johnson Emma C EC Pazdernik Vanessa K VK Jinwala Zeal Z Pakala Shreya R SR Leger Brittany S BS Niarchou Maria M Ehinmowo Michael M Jenkins Greg D GD Batzler Anthony A Pendegraft Richard R Palmer Abraham A AA Zhou Hang H Biernacka Joanna M JM Coombes Brandon J BJ Gelernter Joel J Xu Ke K Hancock Dana B DB Cox Nancy J NJ Smoller Jordan W JW Davis Lea K LK Justice Amy C AC Kranzler Henry R HR Kember Rachel L RL Sanchez-Roige Sandra S

Nature human behaviour 20240417 6

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African America ...[more]

PMID: 38632388

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Project description:Understanding which tobacco products adolescents use first can lead to insights for tobacco prevention interventions and policies. We used cross-sectional data from high school students who reported ever using a tobacco product from the 2017 North Carolina Youth Tobacco Survey (n = 1,053). In multivariable regressions, we examined how demographic and psychosocial factors were associated with adolescents' first product tried and how first product tried was associated with current tobacco use (i.e., no use, use of a single product, use of multiple products) and frequency of tobacco use. Cigarettes (34.8%) and e-cigarettes (33.7%) were the most frequently reported first products tried, followed by cigars (15.6%), smokeless tobacco (10.7%), waterpipe (4.0%), and other tobacco products (i.e., pipe tobacco or some other tobacco product) (1.2%). Demographic differences in adolescents' first product tried existed, with Black adolescents having higher odds of initiating tobacco use via cigars (aOR: 6.17, 95% CI: 3.75, 10.14). Adolescents who initiated tobacco use via cigars (aOR: 2.33, 95% CI: 1.31, 4.13) or smokeless tobacco (aOR: 2.45, 95% CI: 1.18, 5.04) had higher odds of being a multiple current tobacco product user, whereas adolescents who initiated tobacco use via e-cigarettes (aOR: 0.57, 95% CI: 0.34, 0.93) had lower odds of being a multiple current tobacco product user. Additionally, adolescents who initiated tobacco use via smokeless tobacco had higher odds of currently using at least one tobacco product frequently (aOR: 1.90, 95% CI: 1.04, 3.48), while adolescents who initiated tobacco use via e-cigarettes had lower odds of currently using at least one tobacco product frequently (aOR: 0.40, 95% CI: 0.23, 0.70). These findings suggest that most adolescents reported initiating tobacco use via cigarettes or e-cigarettes and that trying certain products first (e.g., cigars, smokeless tobacco) was associated with higher odds of multiple current tobacco product use.

Project description:Background and aimsCannabis use disorder (CUD) during pregnancy has increased dramatically in the United States (US). This study examined the associations between prenatal CUD and adverse neonatal outcomes and heterogeneities in the associations by mothers' tobacco use status and race/ethnicity.DesignPopulation-based, retrospective cohort study.SettingCalifornia, USA.ParticipantsA total of 4.83 million mothers who delivered a live singleton birth during 2001 to 2012 and their paired infants. Data were obtained from mother-infant linked hospital discharge records and birth and death certificates. Identified by ICD-9 codes recorded at delivery, 20 237 mothers had prenatal CUD.MeasurementsNeonatal outcomes included length of gestation, preterm birth, birth weight, admission into neonatal intensive care unit, hospitalization within 1 year of birth, and death within 1 year of birth. Propensity score matching was used to balance maternal, paternal, and infant characteristics in the comparisons between infants exposed and unexposed to prenatal CUD.FindingsCUD increased from 2.8 to 6.9 per 1000 deliveries during 2001 to 2012. Multivariable regressions in matched samples estimated that prenatal CUD was associated with greater odds of being small for gestational age (OR = 1.13, 95% CI = 1.08, 1.18), preterm birth (OR = 1.06, 95% CI = 1.01, 1.12), low birth weight (OR = 1.13, 95% CI = 1.07, 1.20), and death within 1 year of birth (OR = 1.35, 95% CI = 1.12, 1.62). Compared with infants whose mothers were tobacco non-users, infants whose mothers were tobacco users had greater odds of preterm birth, low birth weight, hospitalization, and death in association with prenatal CUD. Compared with infants whose mothers were non-Hispanic White, infants whose mothers were Hispanic had greater odds of hospitalization and death and infants whose mothers were non-Hispanic Black had greater odds of being small for gestational age in association with prenatal CUD.ConclusionPrenatal cannabis use disorder appears to be associated with escalated odds of major adverse neonatal outcomes, with heterogeneities in the associations by mothers' tobacco use status and race/ethnicity.

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Dataset Information

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Publications

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

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