| 1. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 2. |
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| 3. |
- Chen, C., et al.
(författare)
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Associations between psychiatric polygenic risk scores and general and specific psychopathology symptoms in childhood and adolescence between and within dizygotic twin pairs
- 2022
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 63:12, s. 1513-1522
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Tidskriftsartikel (refereegranskat)abstract
- Background Although polygenic risk scores (PRS) predict psychiatric problems, these associations might be attributable to indirect pathways including population stratification, assortative mating, or dynastic effects (mediation via parental environments). The goal of this study was to examine whether PRS-psychiatric symptom associations were attributable to indirect versus direct pathways. Methods The sample consisted of 3,907 dizygotic (DZ) twin pairs. In childhood, their parents rated them on 98 symptoms. In adolescence (n = 2,393 DZ pairs), both the parents and the twins rated themselves on 20 symptoms. We extracted one general and seven specific factors from the childhood data, and one general and three specific factors from the adolescent data. We then regressed each general factor model onto ten psychiatric PRS simultaneously. We first conducted the regressions between individuals (beta) and then within DZ twin pairs (beta(w)), which controls for indirect pathways. Results In childhood, the PRS for ADHD predicted general psychopathology (beta = 0.09, 95% CI: [0.06, 0.12]; beta(w) = 0.07 [0.01, 0.12]). Furthermore, the PRS for ADHD predicted specific inattention (beta = 0.04 [0.00, 0.08]; beta(w) = 0.09 [0.01, 0.17]) and specific hyperactivity (beta = 0.07 [0.04, 0.11]; beta(w) = 0.09 [0.01, 0.16]); the PRS for schizophrenia predicted specific learning (beta = 0.08 [0.03, 0.13]; beta(w) = 0.19 [0.08, 0.30]) and specific inattention problems (beta = 0.05 [0.01, 0.09]; beta(w) = 0.10 [0.02, 0.19]); and the PRS for neuroticism predicted specific anxiety (beta = 0.06 [0.02, 0.10]; beta(w) = 0.06 [0.00, 0.12]). Overall, the PRS-general factor associations were similar between individuals and within twin pairs, whereas the PRS-specific factors associations amplified by 84% within pairs. Conclusions This implies that PRS-psychiatric symptom associations did not appear attributable to indirect pathways such as population stratification, assortative mating, or mediation via parental environments. Rather, genetics appeared to directly influence symptomatology.
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| 4. |
- Clements, C. C., et al.
(författare)
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Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10
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Tidskriftsartikel (refereegranskat)abstract
- Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.
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| 5. |
- Guo, J., et al.
(författare)
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Prenatal exposure to mixture of heavy metals, pesticides and phenols and IQ in children at 7 years of age : The SMBCS study
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prenatal exposure to heavy metals, pesticides and phenols has been suggested to interfere with neurodevelopment, but the neurotoxicity of their mixtures is still unclear. We aimed to elucidate the associations of maternal urinary concentrations of selected chemical mixtures with intelligence quotient (IQ) in children.Methods: Maternal urinary concentrations of selected heavy metals, pesticide metabolites, and phenols were quantified in pregnant women who participated in the Sheyang Mini Birth Cohort Study (SMBCS) from June 2009 to January 2010. At age 7 years, child's IQ score was assessed using the Chinese version of Wechsler Intelligence Scale for Children (C-WISC) by trained pediatricians. Generalized linear regression models (GLM), Bayesian kernel machine regression (BKMR) models and elastic net regression (ENR) models were used to assess the associations of urinary concentrations individual chemicals and their mixtures with IQ scores of the 7-year-old children.Results: Of 326 mother-child pairs, single-chemical models indicated that prenatal urinary concentrations of lead (Pb) and bisphenol A (BPA) were significantly negatively associated with full intelligence quotient (FIQ) among children aged 7 years [β = −2.31, 95% confidence interval (CI): −4.13, −0.48; p = 0.013, sex interaction p-value = 0.076; β = −1.18, 95% CI: −2.21, −0.15; p = 0.025; sex interaction p-value = 0.296, for Pb and BPA, respectively]. Stratified analysis by sex indicated that the associations were only statistically significant in boys. In multi-chemical BKMR and ENR models, statistically significant inverse association was found between prenatal urinary Pb level and boy's FIQ scores at 7 years. Furthermore, BKMR analysis indicated that the overall mixture was associated with decreases in boy's IQ when all the chemicals’ concentrations were at their 75th percentiles or higher, compared to at their 50th percentiles. ENR models revealed that maternal urinary Pb levels were statistically significantly associated with lower FIQ scores (β = −2.20, 95% CI: −4.20, −0.20; p = 0.031).Conclusions: Prenatal exposure to selected chemical mixtures may affect intellectual performance at 7 years of age, particularly in boys. Pb and BPA were suspected as primary chemicals associated with child neurodevelopment.
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| 6. |
- Guo, J., et al.
(författare)
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Urinary bisphenol A concentrations and adiposity measures at age 7 years in a prospective birth cohort
- 2020
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Ingår i: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 251
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) exposure during early life may increase risk of childhood obesity, however, prospective evidence of birth cohort is limited and inconclusive. We aimed to explore the associations of maternal and childhood BPA exposure with child adiposity measures, including body mass index, waist circumference and skinfold thickness and waist to height ratio of children at 7 years. 430 mother-child pairs were examined from a population-based prospective cohort in a rural area of East China. BPA concentrations of spot urine samples were quantified in mothers and their children aged 3 and 7 years. Maternal urinary BPA concentration was significantly positively associated with waist circumference in children aged 7 years (β = 0.508 cm, 95% CI: 0.067, 0.950). These significant associations were not modified by child sex, but they were only observed among girls in sex-stratified analyses. Risk of central obesity related to prenatal BPA exposure was significantly higher in the second and the third tertile than those in the first tertile (odds ratio, OR = 2.510, 95% CI = 1.146, 5.499; OR = 2.584, 95% CI = 1.186, 5.631, respectively; p for trend = 0.022). The present findings suggested that prenatal exposure to BPA may enhance waist circumference of children and thereby increase risk of central obesity in school-age girls.
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| 7. |
- Lu, Guo-Hui, et al.
(författare)
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Potential exposure of perfluorinated compounds to Chinese in Shenyang and Yangtze River Delta areas
- 2011
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Ingår i: Environmental Chemistry. - : CSIRO Publishing. - 1448-2517 .- 1449-8979. ; 8:4, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Environmental contextA total of 21 perfluorinated compounds (PFCs) including PFOS were quantified in river waters, sewage, sea waters, shallow ground waters as well as fish and domestic poultry, focussed on the main river basins in Shenyang and the Yangtze River Delta areas, China. The distribution characteristics of PFCs in the aquatic environment and evaluation of the potential risk for human health via the diet of fish was discussed. Comprehensive research was carried out using the world leading knowledge about PFOS-related chemicals in AIST, Japan to enable reliable evaluation of PFOS risk in Chinese environments, supported by ISO25101. AbstractA total of 21 perfluorinated compounds (PFCs) were quantified in water and biota samples collected from Shenyang in North-east China and the Yangtze River Delta area in East China. The human health risk owing to intake of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) via fish and domestic poultry dietary was evaluated. The total PFC concentration (∑PFC) in water samples from the rivers in Shenyang averaged 5.32ngL-1, with PFOS and PFOA as the predominant compounds. The urban sewage could be the source of PFOS and perfluorohexane sulfonate (PFHxS) in the surface waters. The total PFCs in water samples from the Yangtze River Delta area ranged from 42.4 to 170ngL-1. The highest concentrations of most PFCs were observed in waters from the Shanghai section of the Yangtze River. In the biota samples, PFOS and PFUnDA (perfluoroundecanoic acid) were the most abundant. The acceptable daily intake (ADI) and hazard ratio (HR) values for PFOS and PFOA intake through the diet of fish and poultry in the studied areas were calculated, and showed that the HR values for PFOS and PFOA are all less than 1.0 for both the areas.
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| 8. |
- Mak, Yim Ling, et al.
(författare)
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Perfluorinated Compounds in Tap Water from China and Several Other Countries
- 2009
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:13, s. 4824-4829
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Tidskriftsartikel (refereegranskat)abstract
- The recent development of a sensitive and accurate analytical method for the analysis of 20 perfluorinated compounds (PFCs), including several short-chain PFCs, has enabled their quantification in tap water collected in China, Japan, India, the United States, and Canada between 2006 and 2008. Of the PFCs measured, PFOS, PFHxS, PFBS, PFPrS, PFEtS, PFOSA, N-EtFOSAA, PFDoDA, PFUnDA, PFDA, PFNA, PFHpA, PFHxA, PFPeA, PFBA, and PFPrA were found at detectable concentrations in the tap water samples. The water samples from Shanghai (China) contained the greatest concentrations of total PFCs (arithmetic mean = 130 ng/L), whereas those from Toyama (Japan) contained only 0.62 ng/L. In addition to PFOS and PFOA, short-chain PFCs such as PFHxS, PFBS, PFHxA, and PFBA were found to be prevalent in drinking water. According to the health-based values (HBVs) and advisory guidelines derived for PFOS, PFOA, PFBA, PFHxS, PFBS, PFHxA, and PFPeA by the U.S.EPA and the Minnesota Department of Health, tap water may not pose an immediate health risk to consumers.
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| 9. |
- Martin, J., et al.
(författare)
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Sex-specific manifestation of genetic risk for attention deficit hyperactivity disorder in the general population
- 2018
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 59:8, s. 908-916
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention deficit hyperactivity disorder (ADHD) is more commonly diagnosed in males than in females. A growing body of research suggests that females with ADHD might be underdiagnosed or receive alternative diagnoses, such as anxiety or depression. Other lines of reasoning suggest that females might be protected from developing ADHD, requiring a higher burden of genetic risk to manifest the disorder. Methods: We tested these two hypotheses, using common variant genetic data from two population-based cohorts. First, we tested whether females and males diagnosed with anxiety or depression differ in terms of their genetic risk for ADHD, assessed as polygenic risk scores (PRS). Second, we tested whether females and males with ADHD differed in ADHD genetic risk burden. We used three different diagnostic definitions: registry-based clinical diagnoses, screening-based research diagnoses and algorithm-based research diagnoses, to investigate possible referral biases. Results: In individuals with a registry-based clinical diagnosis of anxiety or depression, females had higher ADHD PRS than males [OR(CI) = 1.39 (1.12-1.73)] but there was no sex difference for screening-based [OR(CI) = 1.15 (0.94-1.42)] or algorithm-based [OR(CI) = 1.04 (0.89-1.21)] diagnoses. There was also no sex difference in ADHD PRS in individuals with ADHD diagnoses that were registry-based [OR(CI) = 1.04 (0.84-1.30)], screening-based [OR(CI) = 0.96 (0.85-1.08)] or algorithm-based [OR(CI) = 1.15 (0.78-1.68)]. Conclusions: This study provides genetic evidence that ADHD risk may be more likely to manifest or be diagnosed as anxiety or depression in females than in males. Contrary to some earlier studies, the results do not support increased ADHD genetic risk in females with ADHD as compared to affected males.
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| 10. |
- Pasman, Joëlle A., et al.
(författare)
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Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers
- 2023
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries.METHODS: This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable.FINDINGS: MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations.INTERPRETATION: The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies.
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