Table 2.

PRS Studies of Imaging Phenotypes in Infancy and Childhood

Article	Participants, N	Age Group	Ancestry	PRS	Findings
Studies on Main Genetic Effects
Xia et al., 2017 (65)	561	6–161 days	Multiancestry	Polygenic scores for GM and WM from adolescent cohort; polygenic scores for ICV from adolescent and adult cohort	Adolescent WM and GM scores showed positive associations with neonatal WM and GM; adult polygenic scores for ICV did not predict neonatal ICV
				PRS for schizophrenia and ASD	PRS did not predict global brain volumes.
Cullen et al., 2019 (68)	194 preterm infants	Mean postmenstrual age at scan 42.6 weeks	Multiancestry	PRS from meta-analysis of genome-wide SNP data for 5 psychiatric disorders (ASD, ADHD, bipolar disorder, MDD, and schizophrenia)	↑PRS—↓ lentiform volume in the mixed ancestral cohort and a European subsample
Khundrakpam et al., 2020 (67)	391 (PING study)	3–21 years	Multiancestry	PRS for ASD	↑ PRS for ASD—↑ cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in the bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus, ↓WM connectivity between the frontal and parietal regions
Morgunova et al., 2021 (74)	142	Neonates (27 ± 13 days)	Multiancestry	ePRS was created based on the DCC coexpression gene network in the PFC.	↑ ePRS—↑ total brain volume (GM and WM, adjusted by ICV)
Alex et al., 2021 (73)	430	Birth–2 years	European	PRS for serum testosterone	↑ PRS—↑ SA development over time in female infants
Cullen et al., 2022 (59)	208	0–6 weeks	European	GPSs for adult subcortical brain volumes	Neonatal volumes of the hippocampus, brainstem, putamen, and thalamus associated with adult GPS
				GPSs for psychiatric disorders ASD, ADHD, schizophrenia, bipolar disorder, MDD, and cross-disorder (including 8 psychiatric disorders: anorexia nervosa, ADHD, ASD, bipolar disorder, MDD, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome)	None of the neonatal brain volumes showed an association with psychiatric GPS.
Le et al., 2022 (66)	257	Postmenstrual age at scan 38–45 weeks	Preliminary analysis: European; secondary; European and Asian	PRS for schizophrenia	↑PRS—↓ right frontal lobe WM, ↓GM and WM superior temporal gyrus volumes and ↓total white matter volume
Studies on Interaction Between Genetic and Environmental Risk
Qiu et al., 2017 (70)	168 (GUSTO) and 85 (US) mother-infant dyads	Neonates: GUSTO (5–14 days), US (postconceptual age at the MRI visit 43.02 ± 2.1 weeks)	GUSTO—Asian; US—mixed ancestry	GPRSMDD	A significant interaction was observed between antenatal maternal depressive symptoms and infant GPRSMDD on right hippocampal volume in the Asian cohort and right amygdala volume in both cohorts. A significant interaction was observed between SES and infant GPRSMDD on right amygdala and hippocampal volumes and shapes in the Asian cohort.
Wang et al., 2017 (50)	164 Mother-offspring dyads (GUSTO)	Neonates (5–14 days)	Asian	A genetic risk score was calculated for individual neonates by summing the number of minor alleles of 19 FKBP5 SNPs.	Neonates with a genetic risk score less than or equal to the median showed a positive association between antenatal maternal depressive symptoms and right hippocampal volume. Neonates with a genetic risk score greater than the median showed a negative association between antenatal maternal depressive symptoms and right hippocampal volume.
Acosta et al., 2020 (71)	105	11–54 days old	European	PRS-MDD	A nonsignificant interaction effect was observed between PRS-MDD and prenatal maternal depressive symptoms on right amygdala volume.
Acosta et al., 2020 (72)	105	11–54 days old	European	PRS-MDD	No significant interaction effects of PRS-MDD with prenatal maternal depressive symptoms were found for infant dorsal striatal volumes. PRS-MDD was more positively associated with caudate volumes in boys compared with girls.
Wu et al., 2020 (75)	161 mother-child dyads (GUSTO)	Neonates (5–14 days)	Asian	A GES was calculated for individuals by summing the number of minor alleles across the SNPs of the gene that were highly correlated with its expression level according to the existing eQTL database.	Positive associations of prenatal maternal depressive symptoms with the hippocampal volume, auditory and prefrontal cortical thickness in neonates high in GESs of the TNF, IL-1, IL-17, chemokine, and TGF family and receptors.
Ursini et al., 2021 (69)	242	10–60 days	European	Fractionated genomic risk scores for schizophrenia based on placental gene expression loci (PlacGRSs)	↑PlacGRSs —↓ neonatal brain volume in singletons and offspring of multiple pregnancies with a history of early-life complications
Qiu et al., 2021 (76)	162 (GUSTO)	Birth–6 years	Asian	A GES was calculated for individuals by summing the number of alleles across the SNPs of the gene that was correlated with TGF-βRI expression level according to the existing eQTL database.	In neonates with a high GES of TGFBR1, higher levels of prenatal maternal depressive symptoms were associated with a smaller right amygdala volume. In children with a low GES of TGFBR1, greater prenatal maternal depressive symptoms predicted greater left and right amygdala volumes at 6 years of age.

ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; ePRS, expression-based polygenic risk score; eQTL, expression quantitative trait loci; GES, genetic expression score; GM, gray matter; GPRSMDD, genomic profile risk score for major depressive disorder; GPS, genome-wide polygenic score; GUSTO, Growing Up in Singapore Toward healthy Outcomes; ICV, intracranial volume; IL, interleukin; MDD, major depressive disorder; MRI, magnetic resonance imaging; PING, Pediatric Imaging, Neurocognition, and Genetics consortium; PFC, prefrontal cortex; PlacGRS, placental genomic risk score; PRS, polygenic risk score; SA, surface area; SES, socioeconomic status; SNP, single nucleotide polymorphism; US, United States; WM, white matter.