Largest-ever analysis reveals genetic links to smoking and alcohol

More than 3,500 genetic variations that may affect smoking and drinking behavior have been identified in a study of nearly 3.4 million people of African, American, Asian and European descent.

The findings, published in Nature December 7¹highlight how increasing sample size and ethnic diversity improves the power of these genome-wide screening analyzes – called genome-wide association studies (GWAS) – to reveal how various traits are linked genes, combinations of genes or mutations.

Smoking and alcohol are significant risk factors for several physical and mental illnesses, including cardiovascular disease 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 are 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 predict a person’s risk of developing nicotine or alcohol addiction using this information, we can intervene early and potentially prevent many deaths.”

Ancestral diversity

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

They identified 3,823 genetic variants associated with smoking or alcohol-related behaviors. Thirty-nine of these were related to the age at which individuals started smoking, 243 to the number of cigarettes smoked per day and 849 to the number of alcoholic beverages consumed per week.

A more inclusive genome project aims to capture all human diversity

Of the total number of associated variants, 721 were identified only by the multi-ancestry GWAS, not by a naïve ancestry model that the authors used for comparison. This suggests that large and diverse population samples greatly increase the power of such studies.

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

However, they also showed that polygenic risk scores – based on a combination of several genetic factors – that were specific to the European ancestry group were poor predictors of smoking and drinking behaviors in other groups of people. ancestry. “Even with these large sample sizes, they just don’t transfer from population to population,” Saunders says.

Environmental influence

The similarity between the ancestors could be partly due to the fact that the vast majority of non-European cohorts included in the study live in the United States and therefore have similar environmental influences – such as public health policies and product availability. based on alcohol and nicotine – says Ananyo Choudhury, a geneticist at the University of the Witwatersrand in Johannesburg, South Africa.

“Epigenetic and environmental factors are really important in turning genes on and off. So maybe it is because of this reason, there are not many [significant] differences,” adds Şehime Temel, who studies medical genetics at Bursa Uludağ University in Turkey.

The analysis also did not include people from the Middle Eastern and Indian populations, where smoking is often prevalent. “Tobacco use is very common [in the Middle East]. There is a huge hookah consumption,” 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 identify more genetic associations.

The researchers acknowledge that their sample does not capture the global diversity of genetic ancestry or geography. “Although this is the largest and most diverse study of smoking and alcohol use phenotypes to date, it did not cover all populations,” Liu says. “In future phases of the study, we will welcome collaborations from other researchers who have access to additional data sets to further expand our studies.”