Dataset Information

Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

ABSTRACT: Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,895 European, 114,420 African American, 44,365 Latin American). 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 behaviors in children, and hundreds of medical outcomes, including HIV infection, heart disease, and pain. This work furthers our biological understanding of TUD and establishes EHR as a source of phenotypic information for studying the genetics of TUD.

SUBMITTER: Toikumo S

PROVIDER: S-EPMC10081388 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous 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 V 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

medRxiv : the preprint server for health sciences 20230918

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,8 ...[more]

PMID: 37034728

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Project description:It is unclear whether the benefits of tobacco control policies extend to pregnant women and infants, especially among racial/ethnic minority and low socioeconomic populations that are at highest risk for adverse birth outcomes.To examine the associations of state cigarette taxes and the enactment of smoke-free legislation with US birth outcomes according to maternal race/ethnicity and education.Using a quasi-experimental approach, we analyzed repeated cross sections of US natality files with 16,198,654 singleton births from 28 states and Washington, DC, between 2000 and 2010. We first used probit regression to model the associations of 2 tobacco control policies with the probability that a pregnant woman smoked (yes or no). We then used linear or probit regression to estimate the associations of the policies with birth outcomes. We also examined the association of taxes with birth outcomes across maternal race/ethnicity and education.State cigarette taxes and smoke-free restaurant legislation.Birth weight (in grams), low birth weight (<2500 g), preterm delivery (<37 weeks), small for gestational age (<10th percentile for gestational age and sex), and large for gestational age (>90th percentile for gestational age and sex).White and black mothers with the least amount of education (0-11 years) had the highest prevalence of maternal smoking during pregnancy (42.4% and 20.0%, respectively) and the poorest birth outcomes, but the strongest responses to cigarette taxes. Among white mothers with a low level of education, every $1.00 increase in the cigarette tax reduced the level of smoking by 2.4 percentage points (-0.0024 [95% CI, -0.0004 to -0.0001]), and the birth weight of their infants increased by 5.41 g (95% CI, 1.92-8.89 g). Among black mothers with a low level of education, tax increases reduced smoking by 2.1 percentage points (-0.0021 [95% CI, -0.0003 to -0.0001]), and the birth weight of their infants increased by 3.98 g (95% CI, 1.91-6.04 g). Among these mothers, tax increases also reduced the risk of having low-birth-weight, preterm, and small-for-gestational-age babies, but increased the risk of having large-for-gestational-age babies. Associations were weaker among higher-educated black women and largely null among higher educated white women and other groups. We did not find evidence for an association of smoke-free restaurant legislation with birth outcomes.Increases in the cigarette tax are associated with improved health outcomes related to smoking among the highest-risk mothers and infants. Considering that US states increase cigarette taxes for reasons other than to improve birth outcomes, these findings are welcome by-products of state policies.

Dataset Information

Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

Publications

Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

Similar Datasets

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