Source/Disclosures
Disclosures: Agerbo reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
January 13, 2021
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Polygenic risk score alone not superior to known risk factors for identifying depression

Source/Disclosures
Disclosures: Agerbo reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Current polygenic risk scores for depression were not more likely to be linked to major depressive disorder than were other known risk factors, according to results of a case-cohort study published in JAMA Psychiatry.

However, in conjunction with other risk factors, they may be helpful in identifying risk, researchers noted.

Esben Agerbo

“Genetics are, in many ways, exactly like any other risk factors — a high genetic liability does not mean doom, but it merely increases risk,” Esben Agerbo, DrMedSc, of the Centre for Integrated Register-based Research and National Centre for Register-Based Research at Aarhus University in Denmark, told Healio Psychiatry. “Furthermore, it is important to report risk (ie, the probability of depression) and not only odds ratios or risk ratios as previous studies have done. Knowing the actual/absolute risk means that one has a solid foundation for evaluating the importance of a risk factor and knowing what can be expected from an intervention.”

According to Agerbo and colleagues, no prior studies have estimated the association of polygenic risk score with the absolute risk for depression, and research is sparse regarding combinations of the polygenic risk score and other significant risk factors, such as socioeconomic status and parental history of psychiatric disorders, in identifying depression risk.

In the current study, the researchers aimed to assess individual and join links of polygenic risk score, parental history and socioeconomic status with relative and absolute risk early-onset depression. They analyzed data of 17,098 individuals with depression and 18,582 individuals randomly selected from the base population, all of whom were included in the iPSYCH2012 sample of all singletons born in Denmark between May 1981 and December 2005. They used Cox proportional hazards regression for case-cohort designs to estimate hazard ratios and absolute risks. Exposures included polygenic risk score for depression; socioeconomic status measured via maternal educational level, maternal marital status and paternal employment; and paternal history of psychiatric disorders. Main outcomes and measures included hospital-based depression diagnosis from emergency, inpatient or outpatient settings.

Results showed significant associations between polygenic risk score, parental history and lower socioeconomic status and increased risk for depression. HRs ranged from 1.32 (95% CI, 1.29-1.35) per one-standard deviation increase in polygenic risk score to 2.23 (95% CI, 1.81-2.65) for maternal history of psychotic or mood disorders. The researchers noted that these risk factors likely do not confound one another, since they observed similar effect sizes among fully adjusted models. By age 30 years, absolute risk for depression differed significantly, depending on an individual’s combination of risk factors. This difference ranged from 1% (95% CI, 0.1-2) among men with high socioeconomic status in the bottom 2% of the polygenic risk score distribution to 23.7% (95% CI, 16.6-30.2) among women in the top 2% of the polygenic risk score distribution who had a parental history of psychiatric disorders.

“These results suggest that, although the [polygenic risk score] alone does not identify risk [for] depression better than known risk factors, it contributes independently of known major risk factors,” Agerbo and colleagues wrote. “Incorporating the depression [polygenic risk score] with other risk factors should improve risk prediction in the general population, especially as [genome-wide association study] sample sizes increase.”