Association of maternal polygenic risk scores for mental illness with perinatal risk factors for offspring mental illness.
Ontology highlight
ABSTRACT:
SUBMITTER: Ratanatharathorn A
PROVIDER: S-EPMC9750139 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Association of maternal polygenic risk scores for mental illness with perinatal risk factors for offspring mental illness.
Ratanatharathorn Andrew A Chibnik Lori B LB Koenen Karestan C KC Weisskopf Marc G MG Roberts Andrea L AL
Science advances 20221214 50
We examined whether genetic risk for mental illness is associated with known perinatal risk factors for offspring mental illness to determine whether gene-environmental correlation might account for the associations of perinatal factors with mental illness. Among 8983 women with 19,733 pregnancies, we found that genetic risk for mental illness was associated with any smoking during pregnancy [attention-deficit hyperactivity disorder (ADHD) and overall genetic risk], breast-feeding for less than ...[more]
Similar Datasets
Project description:ImportanceSeveral recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.ObjectiveTo examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.Design, setting, and participantsThis study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.ExposuresMaternal self-reported smoking during pregnancy, obtained from antenatal visits.Main outcomes and measuresSevere mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.ResultsOf the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.Conclusions and relevanceThis population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
| S-EPMC5539841 | biostudies-literature
Project description:BackgroundGreater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal.MethodsWe undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10-18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs).ResultsMV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size.ConclusionsOur results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.
| S-EPMC8805234 | biostudies-literature
Project description:The COVID-19 pandemic is a global stressor with inter-individually differing influences on mental health trajectories. Polygenic Risk Scores (PRSs) for psychiatric phenotypes are associated with individual mental health predispositions. Elevated hair cortisol concentrations (HCC) and high PRSs are related to negative mental health outcomes. We analyzed whether PRSs and HCC are related to different mental health trajectories during the first COVID lockdown in Germany. Among 523 participants selected from the longitudinal resilience assessment study (LORA), we previously reported three subgroups (acute dysfunction, delayed dysfunction, resilient) based on weekly mental health (GHQ-28) assessment during COVID lockdown. DNA from blood was collected at the baseline of the original LORA study (n = 364) and used to calculate the PRSs of 12 different psychopathological phenotypes. An explorative bifactor model with Schmid-Leiman transformation was calculated to extract a general genetic factor for psychiatric disorders. Hair samples were collected quarterly prior to the pandemic for determining HCC (n = 192). Bivariate logistic regressions were performed to test the associations of HCC and the PRS factors with the reported trajectories. The bifactor model revealed 1 general factor and 4 sub-factors. Results indicate a significant association between increased values on the general risk factor and the allocation to the acute dysfunction class. The same was found for elevated HCC and the exploratorily tested sub-factor "childhood-onset neurodevelopmental disorders". Genetic risk and long-term cortisol secretion as a potential indicator of stress, indicated by PRSs and HCC, respectively, predicted different mental health trajectories. Results indicate a potential for future studies on risk prediction.
| S-EPMC9490720 | biostudies-literature
Project description:ObjectiveIdentifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.MethodsBetween 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.ResultsGreater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.ConclusionsImprovement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
| S-EPMC10113810 | biostudies-literature
Project description:ImportanceMaternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood.ObjectiveTo investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood.Design, setting, and participantsThis population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021.ExposuresMaternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register.Main outcomes and measuresThe main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders.ResultsOf the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08-1.36] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]).Conclusions and relevanceIn this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.
| S-EPMC9012963 | biostudies-literature
Project description:ObjectiveGrowing evidence suggests asthma increases perinatal mental illness risk, but few studies have explored the impact of asthma severity and control. Our objective was to explore the association between asthma severity and control and perinatal mental illness risk and the impact of asthma exacerbations during pregnancy on postpartum mental illness risk.MethodsThis was a population-based retrospective cohort study of all women in Ontario, Canada, from 2005 to 2015 with a singleton live birth who used public drug insurance, excluding women with recent history of mental illness. We constructed modified Poisson regression models to assess the risk of perinatal mental illness, defined as a mood or anxiety, psychotic or substance use disorder, self-harm or other mental illness diagnosed from conception to 365 days postnatally. Models controlled for socio-demographic factors and medical history.ResultsThere were 62,583 women in the cohort (46.7% between 15 - 24 years), of whom 22.7% had asthma (94.3% mild, 5.7% moderate/severe; 86.5% controlled and 13.5% uncontrolled). After adjustment, there was increased risk of perinatal mental illness with mild asthma (adjusted relative risk [RR]: 1.12; 95% confidence interval [CI], 1.09 to 1.16) and moderate/severe asthma (aRR: 1.16; 95% CI, 1.04 to 1.30) compared to no asthma. Controlled asthma (aRR: 1.11; 95% CI, 1.08 to 1.15) and uncontrolled asthma (aRR: 1.19; 95% CI, 1.11 to 1.27) were also associated with increased perinatal mental illness risk compared to no asthma. Women with worsened asthma during pregnancy had the highest risk of postpartum mental illness compared to no change in asthma status (by severity: aRR: 1.57; 95% CI, 1.36 to 1.80; by control: aRR: 1.37; 95% CI, 1.22 to 1.54).ConclusionAsthma is associated with increased risk of perinatal mental illness, particularly in the presence of asthma exacerbations in pregnancy. The results support multidisciplinary collaborative care programmes throughout the perinatal period, especially among women with asthma exacerbations during pregnancy.
| S-EPMC8978216 | biostudies-literature
Project description: Not available
| S-EPMC7998075 | biostudies-literature
Project description:Maternal blood pressure (BP) is associated with variations in fetal weight, an important determinant of neonatal and adult health. However, the association of BP-raising genetic risk with fetal weight is unknown. We tested the associations of maternal BP-raising polygenic risk scores (PRS) with estimated fetal weights (EFWs) at 13, 20, 27, and 40 weeks of gestation. This study included 622 White, 637 Black, 568 Hispanic, and 238 Asian pregnant women with genotype data from the NICHD Fetal Growth Studies. PRS of systolic (SBP) and diastolic BP (DBP) were calculated for each participant based on summary statistics from a recent genome-wide association study. Linear regression models were used to compare mean EFW differences between the highest versus lowest tertile of PRS, adjusting for maternal age, education, parity, genetic principal components and fetal sex. Hispanics in the highest DBP PRS tertile, compared to those in the lowest, had 8.1 g (95% CI: -15.1, -1.1), 32.4 g (-58.4, -6.4) and 119.4 g (-218.1, -20.7) lower EFW at 20, 27 and 40 weeks, respectively. Similarly, Asians in the highest DBP PRS tertile had 137.2 g (-263.5, -10.8) lower EFW at week 40, and those in the highest tertile of SBP PRS had 3.2 g (-5.8, -0.7), 12.9 g (-23.5, -2.4), and 39.8 g (-76.9, -2.7) lower EFWs at 13, 20, and 27 weeks. The findings showed that pregnant women's genetic susceptibility to high BP contributes to reduced fetal growth, suggesting a potential future clinical application in perinatal health.
| S-EPMC8329099 | biostudies-literature
Project description:ImportanceNumerous efforts have been made to include diverse populations in genetic studies, but American Indian populations are still severely underrepresented. Polygenic scores derived from genetic data have been proposed in clinical care, but how polygenic scores perform in American Indian individuals and whether they can predict disease risk in this population remains unknown.ObjectiveTo study the performance of polygenic scores for cardiometabolic risk factors of lipid traits and C-reactive protein in American Indian adults and to determine whether such scores are helpful in clinical prediction for cardiometabolic diseases.Design, setting, and participantsThe Strong Heart Study (SHS) is a large American Indian cohort recruited from 1989 to 1991, with ongoing follow-up (phase VII). In this genetic association study, data from SHS American Indian participants were used in addition to data from 2 large-scale, external, ancestry-mismatched genome-wide association studies (GWASs; 450 865 individuals from a European GWAS and 33 096 individuals from a multi-ancestry GWAS) and 1 small-scale internal ancestry-matched American Indian GWAS (2000 individuals). Analyses were conducted from February 2023 to August 2024.ExposureGenetic risk score for cardiometabolic disease risk factors from 6 traits including 5 lipids (apolipoprotein A, apolipoprotein B, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), and an inflammatory biomarker (C-reactive protein [CRP]).Main outcomes and measuresData from SHS participants and the 2 GWASs were used to construct 8 polygenic scores. The association of polygenic scores with cardiometabolic disease was assessed using 2-sided z tests and 1-sided likelihood ratio tests.ResultsIn the 3157 SHS participants (mean [SD] age, 56.44 [8.12] years; 1845 female [58.4%]), a large European-based polygenic score had the most robust performance (mean [SD] R2 = 5.0% [1.7%]), but adding a small-scale ancestry-matched GWAS using American Indian data helped improve polygenic score prediction for 5 of 6 traits (all but CRP; mean [SD] R2, 7.6% [3.2%]). Lipid polygenic scores developed in American Indian individuals improved prediction of diabetes compared with baseline clinical risk factors (area under the curve for absolute improvement, 0.86%; 95% CI, 0.78%-0.93%; likelihood ratio test P = 3.8 × 10-3).Conclusions and relevanceIn this genetic association study of lipids and CRP among American Indian individuals, polygenic scores of lipid traits were found to improve prediction of diabetes when added to clinical risk factors, although the magnitude of improvement was small. The transferability of polygenic scores derived from other populations is still a concern, with implications for the advancement of precision medicine and the potential of perpetuating health disparities, particularly in this underrepresented population.
| S-EPMC11904716 | biostudies-literature
Project description:BackgroundPolygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry.ResultsWe introduce the polygenic transcriptome risk score (PTRS), which is based on predicted transcript levels (rather than SNPs), and explore the portability of PTRS across populations using UK Biobank data.ConclusionsWe show that PTRS has a significantly higher portability (Wilcoxon p=0.013) in the African-descent samples where the loss of performance is most acute with better performance than PRS when used in combination.
| S-EPMC8759285 | biostudies-literature