Study Finds Genetic Link To Smoking And Drinking

Nature published information from a study titled: “Largest-ever analysis finds genetic links to smoking and drinking”. More than 3,500 genetic variations that potentially affect smoking and drinking behavior have been identified in a study involving almost 3.4 million people with African, American, East Asian, and European ancestry.

The findings, published in Nature on December 7, 2022, highlight how increasing sample size and ethnic diversity improves the power of such genome-screening analyses – called genome-wide association studies (GWAS) – to reveal how various traits are linked to genes, combinations of genes or mutations.

Smoking and drinking are important risk factors for several physical and mental illnesses, including cardiovascular diseases and psychiatric disorders. Although both behaviors are influenced by environmental and social factors, there is evidence that genetics can affect tobacco and alcohol consumption. 

“We’re at a stage where genetic discoveries are being translated” into clinical applications, says study co-author Dajiang Liu, a statistic geneticist at Penn State College of Medicine in Hershey, Pennsylvania. “If we can forecast someone’s risk of developing nicotine or alcohol dependence using this information, we can intervene early and potentially prevent a lot of deaths.”

Scientists use GWAS to find genetic ties to diseases or behaviors by comparing genetic sequences in large numbers of people. But so far, most of these studies have focused on European populations. Dajiang Liu and his colleagues constructed a model that incorporated the genomic data of 3,383,199 people, 21% of whom had non-European ancestry.

They identified 3,823 genetic variants that were associated with smoking or drinking with number of cigarette smoked per day and 849 with the number of alcoholic drinks consumed per week.

Of the total number of associated variants, 721 were identified only by the multi-ancestry study, and not by an ancestral-naive model that the authors used for comparison. This suggests that large and diverse population samples significantly increase the power of such studies.

The researchers found that the majority of genetic associations for drinking and smoking have similar effects across the different ancestries. “We also find similar heritability estimates [for the traits] across the ancestries… suggesting that generally, the genetic architecture of these behaviors is similar across ancestries,” said Gretchen Saunders, a psychologist at the University of Minnesota, Minneapolis and co-author of the paper.

However, they also showed that polygenetic risk scores – based on a combination of multiple genetic factors – that were specific to the European ancestry group were poor predictions of smoking and drinking behaviors in other ancestry groups.

The similarity across ancestries could be partly because the vast majority of non-European cohorts included in the study live in the United States, and therefore have been similar environmental influences – such as public-health policies and the availability of alcohol and nicotine products – says Ananyo Chowdhury, a geneticist at the University of the Witwiterstrand in Johannesburg, South Africa.

The analysis also didn’t include people from Middle Eastern and Indian populations, in which smoking is often prevalent. “Tobacco use is very common [in the Middle East]. There is a huge consumption of the shisha waterpipe, says Mahmut Ergören, a medical biologist at the Near East University in Nicosia, Cyprus. He adds that including these populations in the analysis would improve its accuracy and help to identify more genetic associations. 

The researchers acknowledge that their sample does not capture global diversity in genetic ancestry or geography. “While being the largest and most ancestrally diverse study of smoking and drinking phenotypes so far, it has not covered all populations,” said Liu. “In future phases of the study, we will welcome collaborations from other investigators who have access to additional data sets to further expand our studies.”

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