Effects of Polygenic Risk Score, Childhood Trauma and Resilience on Depressive Symptoms in Chinese Adolescents in A Three-year Cohort Study

Abstract Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother–infant dyads (44 female, 11–54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.

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Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis: Genetic Risk and Outcome of Psychosis (GROUP) cohort study

Journal of Psychosomatic Research ◽

10.1016/j.jpsychores.2020.109968 ◽

2020 ◽

Vol 132 ◽

pp. 109968 ◽

Cited By ~ 3

Author(s):

Tesfa Dejenie Habtewold ◽

Md. Atiqul Islam ◽

Edith J. Liemburg ◽

Richard Bruggeman ◽

Behrooz Z. Alizadeh ◽

...

Keyword(s):

Cohort Study ◽

Risk Score ◽

Genetic Risk ◽

Polygenic Risk Score ◽

Affective Psychosis ◽

Polygenic Risk ◽

Glycemic Level

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Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants

BMJ ◽

10.1136/bmj.k4168 ◽

2018 ◽

pp. k4168 ◽

Cited By ~ 32

Author(s):

Loes CA Rutten-Jacobs ◽

Susanna C Larsson ◽

Rainer Malik ◽

Kristiina Rannikmäe ◽

Cathie L Sudlow ◽

...

Keyword(s):

Cohort Study ◽

Risk Score ◽

Genetic Risk ◽

Cox Regression ◽

Healthy Lifestyle ◽

Lifestyle Factors ◽

Polygenic Risk Score ◽

Uk Biobank ◽

Polygenic Risk ◽

Increased Risk

AbstractObjectiveTo evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.DesignProspective population based cohort study.SettingUK Biobank Study, UK.Participants306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.Main outcome measureHazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10−5to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise.ResultsDuring a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10−8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10−13. The association with lifestyle was independent of genetic risk stratums.ConclusionIn this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

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Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations

The Lancet Respiratory Medicine ◽

10.1016/s2213-2600(19)30144-4 ◽

2019 ◽

Vol 7 (10) ◽

pp. 881-891 ◽

Cited By ~ 15

Author(s):

Juncheng Dai ◽

Jun Lv ◽

Meng Zhu ◽

Yuzhuo Wang ◽

Na Qin ◽

...

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

Prospective Cohort Study ◽

Risk Score ◽

Prospective Cohort ◽

Large Scale ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Chinese Populations

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A Polygenic Risk Score Associated with Measures of Depressive Symptoms Among Older Adults

Biodemography and Social Biology ◽

10.1080/19485565.2014.952705 ◽

2014 ◽

Vol 60 (2) ◽

pp. 199-211 ◽

Cited By ~ 19

Author(s):

Morgan E. Levine ◽

Eileen M. Crimmins ◽

Carol A. Prescott ◽

Drystan Phillips ◽

Thalida E. Arpawong ◽

...

Keyword(s):

Older Adults ◽

Depressive Symptoms ◽

Risk Score ◽

Polygenic Risk Score ◽

Polygenic Risk

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Childhood trajectories of internalising and externalising problems associated with a polygenic risk score for neuroticism in a UK birth cohort study

10.1101/2021.12.15.21267397 ◽

2021 ◽

Author(s):

Ilaria Costantini ◽

Hannah Sallis ◽

Daniel Major-Smith ◽

Kate Tilling ◽

Rebecca M Pearson ◽

...

Keyword(s):

Cohort Study ◽

Birth Cohort ◽

Risk Score ◽

Psychological Outcomes ◽

Birth Cohort Study ◽

Polygenic Risk Score ◽

Mixed Effect ◽

Polygenic Risk ◽

Externalising Problems ◽

Internalising Problems

Neuroticism represents a personality disposition towards experiencing negative emotions more frequently and intensely. Longitudinal studies suggest that neuroticism increases risk of several psychological and physical problems. Improved understanding of how this trait manifests in early life could help inform preventative strategies in those liable to neuroticism. This study explored how a polygenic risk score (PRS) for neuroticism is expressed from infancy to late childhood across various psychological outcomes and how it associates with trajectories of internalising and externalising problems from ages 4-11 in the Avon Longitudinal Study of Parents and Children (N=5,279). We employed multivariable linear and ordinal regression models to estimate associations between a child neuroticism PRS and psychological outcomes. A three-level mixed-effect model was employed to characterise child internalising and externalising trajectories and estimate how a child PRS associated with both their overall levels and rates of change. We found evidence that the PRS for neuroticism was associated with a more sensitive temperament in early infancy in addition to higher emotional and behavioural problems and a higher risk of being diagnosed with a variety of clinical disorders, particularly anxiety disorders, in childhood. We also found strong evidence that the PRS for neuroticism was associated with overall levels of internalising and externalising trajectories, with a larger magnitude of effect on the internalising trajectory. The PRS was also associated with slower rates of reduction of internalising problems. Our findings using a large, well-characterised birth cohort study suggest that phenotypic manifestations of a PRS for adult neuroticism can be detected as early as in infancy and that this PRS associates with several mental health problems and differences in emotional trajectories across childhood.

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