A massive study finds genetic links to smoking and drinking

An international group of researchers have conducted a study and identified more than 3,500 genetic variations that potentially affect smoking and drinking behaviour. 

The study involved almost 3.4 million people from diverse backgrounds, including African, American, East Asian and European ancestry.

The results were published in Nature on December 7. They emphasise that increasing the sample size and ethnic diversity improves the power of genome-wide association studies (GWAs) such as these, showing that various traits are linked to genes, combinations of genes or mutations.

The scientific community already considers smoking and drinking as risk factors for several physical and mental illnesses, including cardiovascular diseases and psychiatric disorders.

Despite the fact that both smoking and drinking are affected by environmental and social factors, evidence points to genetics as another underlying influence in tobacco and alcohol consumption.

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“We’re at a stage where genetic discoveries are being translated into clinical [applications],” says study co-author Dajiang Liu, a statistical 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.”

A diverse set of subjects

Scientists compare genetic sequences in large numbers of people using GWAs to find genetic ties to diseases or behaviours. However, in the past, these studies have largely relied on European individuals.

This time around, Liu and his colleagues used a model that made use of the genomic data of 3,383,199 people (almost 3.4 million), and 21 percent of this population had non-European ancestry.

The researchers came up with 3,823 genetic variants that were associated with smoking or drinking behaviours, 39 of which were linked with the age at which people took up smoking, 243 with the number of cigarettes smoked per day and 849 with the number of alcoholic drinks consumed per week.

At least 721 associated variants out of the total were picked up only by the multi-ancestry GWAs, as opposed to an ancestry-naive model the researchers used for comparison. This means that large and diverse population samples improve upon and increase the power of such studies.

According to the researchers, 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 behaviours is similar across ancestries,” says Gretchen Saunders, a psychologist at the University of Minnesota, Minneapolis, and co-author of the paper.

On the other hand, the researchers also demonstrated that polygenic risk scores that were specific to the European ancestry group did not properly predict smoking and drinking behaviours in other ancestry groups. 

“Even with these big sample sizes, they just do not transfer across populations,” says Saunders.

Environmental effects on smoking and drinking

One of the authors, Ananyo Choudhury, a geneticist at the University of the Witwatersrand in Johannesburg, South Africa, explains the similarity across ancestries partly with the vast majority of non-European cohorts living in the US, and have similar environmental influences, such as public-health policies and the availability of alcohol and nicotine products.

“Epigenetic and environmental factors are really important to turn off and turn on the genes. So maybe it’s because of that reason, there aren’t many [significant] differences,” adds Sehime Temel, who studies medical genetics at Bursa Uludag University, Türkiye.

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The analysis failed to incorporate people from Middle Eastern and Indian populations, where smoking is often prevalent.

“Tobacco use is very common [in the Middle East]. There is a huge consumption of the shisha waterpipe” says Mahmut Ergoren, a medical biologist at the Near East University in Lefkosa, Turkish Republic of Northern Cyprus. 

Ergoren believes that adding these populations would sharpen the study’s accuracy and help to nail down more genetic associations.

The researchers admit that even larger than many, their sample still doesn’t allow for the most diverse results possible in terms of 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,” says Liu. “In future phases of the study, we will welcome collaborations from other investigators who have access to additional datasets to further expand our studies.”