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- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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- Czamara, D, et al.
(författare)
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Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:19
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.
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- Neumann, A, et al.
(författare)
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A genome-wide association study of total child psychiatric problems scores
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8, s. e0273116-
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Tidskriftsartikel (refereegranskat)abstract
- Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
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