Clara Albiñana’s research while affiliated with Aarhus University and other places

Importance Adverse perinatal outcomes are common challenges for mothers and their newborns. Epidemiological studies indicate that mothers with psychiatric and neurodevelopmental disorders are at an increased risk of adverse pregnancy and neonatal outcomes; however, the underlying mechanisms behind these associations remain inadequately understood. Objective To investigate whether perinatal risk factors are driven by maternal genetic susceptibility to multiple psychiatric and neurodevelopmental disorders. Design, setting and participants This nationwide population-based case control study identified 14,917 primiparous mothers with available genetic information, born between 1981 and 2008, from the iPSYCH cohort, which is nested in the Danish National Registers. Exposures Eight genome-wide polygenic scores (PGS) for psychiatric and neurodevelopmental disorders in mothers, including ADHD, autism spectrum disorder (ASD), schizophrenia, depression, anxiety, bipolar disorder, obsessive-compulsive disorder and anorexia nervosa, were calculated using LDPred2. Main outcomes and measures Six pregnancy related and four neonatal related risk factors were obtained from the Danish Medical Birth Registry. Odds ratios (ORs) and 95% CIs were estimated, adjusted for the year of delivery and the first 10 genetic principal components. Results Of 14,917 mothers, the mean age at childbirth was 24.9 years (standard deviation [SD]=3.9). Per SD increase in the PGS for ADHD (OR=1.07 [95%CI 1.00-1.14]), anxiety (1.10 [1.03-1.18]) and depression (1.12 [1.05-1.20]) were associated with maternal smoking exceeding 10 cigarettes per day during the early pregnancy. Stronger associations were observed for the depression PGS in relation to younger age at first birth (i.e. < 20 years; 1.15 [1.07-1.23]), mandatory education (1.15 [1.11-1.19]), and non ohabitation status during pregnancy (1.07 [1.02-1.12]), compared to other PGS. Schizophrenia PGS was associated with reduced odds of maternal obesity (0.88 [0.84-0.93]) during early pregnancy. In contrast, little evidence was found for associations between maternal PGS for psychiatric and neurodevelopmental disorders and neonatal related risk factors. We observed comparable associations when the analyses excluded mothers with any psychiatric or neurodevelopmental disorders prior to the conception date. Conclusions and relevance High genetic loading for psychiatric and neurodevelopmental disorders may partly explain the observed phenotypic associations between maternal mental illness and perinatal risk factors, particularly pregnancy related factors, but it is less likely to account for associations with neonatal related factors. Alternative mechanisms, e.g., psychological stress and medical treatment for psychiatric and neurodevelopmental disorders, should be further explored.

Background Previous research has shown that females who use hormonal contraception are at increased risk of developing depression, and that the risk is highest among adolescents. While this finding could reflect age‐specific effects of exogenous hormones on mental health, genetic liability for mental disorders could be confounding the association. Our goal was to test the plausibility of this hypothesis by determining whether polygenic liabilities for major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD) are associated with younger age at hormonal contraception initiation. Methods We conducted a cohort study using data from the Danish iPSYCH2015 sub‐cohort, a representative sample of people born in Denmark between May 1981 and December 2008. Polygenic scores (PGSs) for MDD, BD, SCZ, and ADHD were created using the most recent genome‐wide association study meta‐analyses from the Psychiatric Genomics Consortium. Associations between PGSs and hormonal contraception initiation in the following age categories: 10–14, 15–19, 20–24, and 25+ were examined via Cox regression. We examined any hormonal contraception, oral contraception, and non‐oral contraception. Results PGS‐MDD and PGS‐ADHD showed the strongest associations with hormonal contraception initiation at age 10–14 (PGS‐ADHD: HR = 1.21 [95% CI = 1.16–1.27], p = 6.16 x 10 ⁻¹⁸ ; PGS‐MDD: 1.21 [1.16–1.27], p = 1.22 x 10 ⁻¹⁷ ). The associations then steadily decreased as age at hormonal contraception initiation increased. Both PGS‐MDD and PGS‐ADHD were also associated with initiation at ages 15–19, but not at 20–24 or 25+. PGS‐BD and PGS‐SCZ were also associated, albeit not as strongly, with initiation at age 10–14 only (PGS‐BD: 1.07 [1.02–1.13], p = 6.87 × 10 ⁻³ ; PGS‐SCZ: 1.09 [1.04–1.14], p = 8.61 × 10 ⁻⁴ ). Conclusions and Relevance These results suggest that genetic confounding could explain some of the association between early hormonal contraception use and depression. Where possible, researchers studying this important topic should account for possible confounding by genetic liability for mental disorders.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981–2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%–100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.

Vitamins play an intrinsic role in human health and are targets for clinical intervention through dietary or pharmacological approaches. Biomarkers of vitamin status are complex traits, measurable phenotypes that arise from an interplay between dietary and other environmental factors with a genetic component that is polygenic, meaning many genes are plausibly involved. Studying these genetic influences will improve our knowledge of fundamental vitamin biochemistry, refine estimates of the effects of vitamins on human health, and may in future prove clinically actionable. Here, we evaluate genetic studies of circulating and excreted biomarkers of vitamin status in the era of hypothesis-free genome-wide association studies (GWAS) that have provided unprecedented insights into the genetic architecture of these traits. We found that the most comprehensive and well-powered GWAS currently available were for circulating status biomarkers of vitamin A, C, D, and a subset of the B vitamins (B9 and B12). The biology implicated by GWAS of measured biomarkers of each vitamin is then discussed, both in terms of key genes and higher-order processes. Across all major vitamins, there were genetic signals revealed by GWAS that could be directly linked with known vitamin biochemistry. We also outline how genetic variants associated with vitamin status biomarkers have been already extensively used to estimate causal effects of vitamins on human health outcomes, which is particularly important given the large number of randomized control trials of vitamin related interventions with null findings. Finally, we discuss the current evidence for the clinical applicability of findings from vitamin GWAS, along with future directions for the field to maximize the utility of these data.

Background The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care. Methods Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 ( N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions. Results We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21). Conclusions We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Objective Eating disorders (EDs) are serious psychiatric disorders with an estimated 3.3 million healthy life-years lost worldwide yearly. Understanding the course of illness, diagnostic transitions and remission, and their associated genetic correlates could inform both ED etiology and treatment. The authors investigated occurrences of ED transitions and presumed remission and their genetic correlates as captured by polygenic scores (PGSs) in a large Danish register-based cohort. Methods The sample compromised of 10,565 individuals with a diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (EDNOS) with at least two registered hospital contacts between 1995 and 2018. Based on medical records, occurrence of diagnostic transitions and periods of presumed remission were identified. Associations between 422 PGS and diagnostic transitions and presumed remission were evaluated using Cox proportional hazard models. Results A minority of ED cases (14.1%-23.1%) experienced a diagnostic transition. Presumed remission ranged between 86.9%-89.8%. Higher (one SD increase) PGS for major depressive disorder and multisite chronic pain were positively associated with transitioning from AN to either BN or EDNOS. Higher PGS on a measure of body fat percentage and financial difficulties were positively associated with presumed remission from AN. Higher PGS for mood swings was positively associated with presumed remission from EDNOS whereas higher PGS for health rating showed the opposite. Conclusions The authors found that most ED patients did not experience diagnostic transitions but were more likely to experience a period of presumed remission. Both diagnostic transitions and presumed remission have significant polygenic component.