Estimating the impact of transmitted and non-transmitted psychiatric and neurodevelopmental polygenic scores on youth emotional problems.
Amy ShakeshaftJoanna MartinCharlotte A DennisonLucy RiglinCathryn M LewisMichael C O'DonovanAnita ThaparPublished in: Molecular psychiatry (2023)
Anxiety and depression (emotional disorders) are familial and heritable, especially when onset is early. However, other cross-generational studies suggest transmission of youth emotional problems is explained by mainly environmental risks. We set out to test the contribution of parental non-transmitted genetic liability, as indexed by psychiatric/neurodevelopmental common polygenic liability, to youth emotional problems using a UK population-based cohort: the Millennium Cohort Study. European (N = 6328) and South Asian (N = 814) ancestries were included, as well as a subset with genomic data from both parents (European: N = 2809; South Asian: N = 254). We examined the association of transmitted (PGS T ) and non-transmitted polygenic scores (PGS NT ) for anxiety, depression, bipolar disorder and neurodevelopmental disorders (attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD], schizophrenia) with youth emotional disorder and symptom scores, measured using the parent- and self-reported Strengths and Difficulties Questionnaire emotional subscale at 6 timepoints between ages 3-17 years. In the European sample, PGS T for anxiety and depression, but not bipolar disorder, were associated with emotional disorder and symptom scores across all ages, except age 3, with strongest association in adolescence. ADHD and ASD PGS T also showed association across ages 11-17 years. In the South Asian sample, evidence for associations between all PGS T and outcome measures were weaker. There was weak evidence of association between PGS NT for anxiety and depression and age 17 symptom scores in the South Asian sample, but not in the European sample for any outcome. Overall, PGS T for depression, anxiety, ADHD and ASD contributed to youth emotional problems, with stronger associations in adolescence. There was limited support for non-transmitted genetic effects: these findings do not support the hypothesis that parental polygenic psychiatric/neurodevelopmental liability confer risk to offspring emotional problems through non-transmitted rearing/nurture effects.
Keyphrases
- attention deficit hyperactivity disorder
- mental health
- autism spectrum disorder
- bipolar disorder
- depressive symptoms
- intellectual disability
- physical activity
- major depressive disorder
- working memory
- sleep quality
- type diabetes
- metabolic syndrome
- deep learning
- dna methylation
- machine learning
- climate change
- high fat diet
- human health
- adipose tissue
- big data
- electronic health record