Herasight offered couples undergoing IVF a genetic score for selecting embryos based on depression risk and released a preprint evaluating the score in siblings
Herasight offered couples undergoing IVF a genetic score for selecting embryos based on depression risk and released a preprint evaluating the score in siblings
On 2 November, Herasight launched MDD-PGT, a polygenic score for depression risk that combines the contributions of many small differences in DNA. In October, the company released NeuroRisk, an embryo test for rare damaging DNA variants. The company described its evaluation of the score in a preprint (a manuscript awaiting peer review), using DNA and medical records from UK Biobank and data from ABCD, a US study of children.
In UK Biobank, MDD-PGT explains 7,0% of the variation in susceptibility to depression. A benchmark score that the company built using data from the largest genetic study of depression available at the time, conducted in 2025 by the Psychiatric Genomics Consortium, explains 4,6%. The proportion explained by MDD-PGT is approximately 50% higher.
Herasight attributes the weaker performance of previous scores to noise in depression diagnoses. Of the people classified as having depression in the first UK Biobank questionnaire, only 47,7% met the criteria when surveyed again six years later. Adjusting for this noise raises the proportion explained to 9,1% for MDD-PGT and 6,1% for the benchmark. To build the score, the company first inferred depression status for participants in several biobanks whose records were missing or unreliable, then added data on related traits. Depression and anxiety, for example, share much of their genetic basis.
Embryo selection involves choosing among embryos from the same couple, so the score was tested in full siblings. In the overall sample, without accounting for family relationships, people with high scores tend to grow up in different family environments from those with low scores. Their parents, for example, are more likely to have had depression. Siblings share parents and a home, and the company says their differences reflect “mostly the random draw of which genes each inherited, which is the same variation parents choose among when comparing their own embryos.” The association between the score and depression persisted within sibling groups, at 103% of the association in the overall sample. Its association with lower educational attainment almost disappeared among siblings, indicating that the analysis can detect the influence of the family environment.
In ABCD, whose data were not used to build the score, MDD-PGT explains 39% more variation in susceptibility to depression than the benchmark. Among the 10% of children with the highest scores, 23% reported suicidal thoughts by age 14, compared with 7% among the 10% with the lowest scores.
Because the score retained its predictive strength among siblings, the company concludes that its accuracy carries over to embryo selection. According to a calculation in its blog, for a couple with five embryos and no family history of depression, a daughter's expected lifetime risk of depression would range from 13% if they selected the embryo with the lowest score to 27% if they selected the one with the highest score, averaged across many such selections. The calculation assumes a baseline risk of 19,5% for a woman by age 85.
In 2021, the International Society of Psychiatric Genetics stated that polygenic scores for psychiatric conditions, including depression, were insufficiently accurate for clinical use. It also noted that these scores are associated with multiple conditions, so selection based on one condition could affect others. The preprint examines whether the score is specific to depression: if it had shifted toward predicting anxiety or neuroticism (a tendency toward emotional instability), its improvement over the benchmark would be greater for those traits than for depression. This was the pattern in the overall sample. Among siblings in UK Biobank, however, the improvements were of a similar magnitude: associations with MDD-PGT were stronger than those with the benchmark by 20% for anxiety, 33% for neuroticism and 24% for depression. The authors acknowledge that some shift toward neuroticism is possible.