An atlas of genetic correlations between gestational age and common psychiatric disorders

Yao, Yao; Li, Chune; Meng, Peilin; Cheng, Bolun; Cheng, Shiqiang; Liu, Li; Yang, Xuena; Jia, Yumeng; Wen, Yan; Zhang, Feng

doi:10.1002/aur.2719

Cited by 6 publications

(6 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on stratified linkage disequilibrium score regression (SLDSC) with the baseline-LD model 2 , we calculated single trait SNP heritability for IBDs and PBC. Then bivariate LDSC 56 were conducted to evaluate genetic correlations between IBDs and PBC 57 .…”

Section: Methodsmentioning

confidence: 99%

Rare Comorbidity between Inflammatory Bowel Disease and Primary Biliary Cholangitis: Evidence from Causality, Shared Genetic Architecture and Transcriptomics

Huang

Jiang²,

Zeng

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundClinical studies have found comorbidity between Inflammatory Bowel Disease (IBD) and primary sclerosing cholangitis (PSC). Primary biliary cholangitis (PBC) is another autoimmune liver disease but the coexistence of IBD and PBC is rare. Whether there exists comorbidity between IBD and PBC and potential mechanism remains unclear.MethodsWe assessed the casual effect between PBC and IBD, i.e., Crohn Disease (CD) and Ulcerative Colitis (UC) independently based on genome-wide association studies (GWAS) summary statistics. By leveraging data from GWAS data, Bulk tissue RNA sequencing (bulk RNA-seq) data, and Single-cell RNA sequencing (scRNA-seq) dataset, we investigated the shared genetic architecture between IBDs and PBC. The transcriptomic expressions of shared genes were explored in patients with IBD (intestinal biopsies) and PBC (peripheral CD4+T cells).ResultWe found a bidirectional causal relationship for PBC and IBDs using Mendelian randomization. The IBDs had been considered as the protective factors on PBC (0.87[95% confidence interval (CI): 0.81-0.93],P= 8.72e-5, vice versa (0.91[95% CI: 0.81-0.93],P= 2.65e-09). We find a consistent negative genetic correlation between PBC and IBD (LDSC:rg= -0.2245,P= 2.89e-5). Cross-trait analysis yielded 9 shared risk SNPs and 7 nearest genes. In transcriptome analysis, we observed significant (P< 0.05) differences expression in intestinal biopsies (PGAP3andDENND1B) and in peripheral CD4+T cells (PTPN11andPNMT). We identified shared tissue-specific heritability enrichment for PBC and IBD (including CD not UC) in lung, spleen and cells EBV-transformed lymphocytes and identified shared cell type-level enrichment for IBD, CD and PBC in type 1 dendritic cells, natural killer cells, CD8+cytotoxic T lymphocytes in lung and activated CD8+T cell in spleen.ConclusionOur study indicates that IBD and PBC are protective factors for each other and shared genetic architecture may contribute to the negative genetic correlation. These findings may explain the rare comorbidity between IBD and PBC.

show abstract

Section: Methodsmentioning

confidence: 99%

Rare Comorbidity between Inflammatory Bowel Disease and Primary Biliary Cholangitis: Evidence from Causality, Shared Genetic Architecture and Transcriptomics

Huang

Jiang²,

Zeng

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The same study did not find strong evidence in either direction for being breastfed as a baby or place of birth in UK (Soler Artigas et al., 2022 ). Another study did not find strong evidence of a causal effect of genetic liability to gestational duration on ADHD (Yao et al., 2022 ).…”

Section: Birthweight Gestational Age and Environmental Exposuresmentioning

confidence: 99%

Mendelian randomisation studies of Attention Deficit Hyperactivity Disorder

Riglin

Stergiakouli

2022

JCPP Advances

View full text Add to dashboard Cite

Background Observational studies have found Attention Deficit Hyperactivity Disorder (ADHD) to be associated with an increased risk of adverse outcomes as well as with early risk factors; however it is not clear whether these associations reflect causal effects. Alternatives to traditional observational studies are needed to investigate causality: one such design is Mendelian randomization (MR), which uses genetic variants as instrumental variables for the exposure. Methods In this review we summarise findings from approximately 50 studies using MR to examine potentially causal associations with ADHD as either an exposure or outcome. Results To‐date, few MR ADHD studies have investigated causal evidence with other neurodevelopmental, mental health and neurodegenerative conditions but those that have suggest a complex relationship with autism, some evidence of a causal effect on depression and limited evidence of a causal effect on neurodegenerative conditions. For substance use, MR studies provide evidence consistent with a causal effect of ADHD on smoking initiation, but findings for other smoking behaviours and cannabis use are less consistent. Studies of physical health suggest bidirectional causal effects with higher body mass index, with stronger effects for childhood obesity, as well as some evidence of causal effects on coronary artery disease and stroke in adults and limited evidence of causal effects on other physical health problems or sleep. Studies suggest bidirectional relationships between ADHD and socio‐economic markers and provide some evidence that low birthweight may be a causal risk factor for ADHD, while bidirectional evidence has been found for some environmental factors. Finally, there is emerging evidence of bidirectional causal links between ADHD genetic liability and biological markers of human metabolism and inflammation. Conclusions While MR has advantages over traditional observational designs in addressing causality, we discuss limitations of current ADHD studies and future directions, including the need for larger genome‐wide association studies (and using samples of different ancestries), and for triangulation with different methods.

show abstract

“…According to recommendation, we set the parameter that the population prevalence and observed sample prevalence as 0.0003 and 0.63 separately to convert observed scale heritability to the liability-scale 46 . Then we performed bivariate LDSC 47 without constraining the intercept to estimate r g value, representing genetic correlations between MS and BMI and selected the suggestive (P < 0.05) genetic associations as the significant correlation 48 . Sensitivity analysis were conducted based on LDSC with the single-trait heritability intercept constrained.…”

Section: Heritability and Genetic Correlationmentioning

confidence: 99%

“…We undertook Mendelian Randomization analysis including main five MR methods, MR-Egger 56 , inverse variance weighting (IVW) 57 , weighted median 58 ,weighted mode 59 and Generalized Summary-data-based Mendelian Randomization (GSMR) 60 with different assumptions about horizontal pleiotropy. Briefly, when there is one single genetic variant, the Wald ratio is a way to calculate the causative effect between the exposure and the outcome 48 . Using the meta-analysis approach, IVW analysis can estimate causal effects of two phenotype.…”

Section: Mr Analysesmentioning

confidence: 99%

Investigating shared genetic architecture between obesity and multiple sclerosis

Zeng

Jiang

Huang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background and aims Observational studies have suggested a complex relationship between obesity and multiple sclerosis (MS). However, the role of genetic factors in the comorbidity and whether obesity exist consistent shared genetic relationships with MS, remains unclear. Our study aims to investigate the extent of shared genetic architecture underlying obesity and MS. Methods Based on genome-wide association studies (GWAS) summary statistics, we investigate the genetic correlation by the linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). The casualty was identified by using bidirectional Mendelian randomization. Linkage disequilibrium score regression in specifically expressed genes (LDSC-SEG) and multi-marker analysis of GenoMic annotation (MAGMA) were utilized to investigate single-nucleotide polymorphisms (SNP) enrichment in the tissue and cell-type levels. We then identified shared risk SNPs using cross-trait meta-analyses and Heritability Estimation from Summary Statistics (ρ-HESS). We further explore the potential functional genes for BMI and MS using summary-data-based Mendelian randomization (SMR). Result We found significantly positive genetic correlation and 18 novel shared genetic SNPs were identified in cross-trait meta-analyses. We found the causality of BMI on MS using Mendelian randomization, but slight inconsistent evidence for the causality of MS on BMI. We observed tissue-specific level SNP heritability enrichment for BMI in 9 tissues and MS in 4 tissues, and in cell-type-specific level SNP heritability enrichment 12 consistent cell types were identified for BMI and MS in brain, spleen, lung and whole blood. Conclusion Our study identifies the genetical correlation and shared risk SNPs between BMI and MS. These findings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trials.

show abstract

An atlas of genetic correlations between gestational age and common psychiatric disorders

Cited by 6 publications

References 61 publications

Rare Comorbidity between Inflammatory Bowel Disease and Primary Biliary Cholangitis: Evidence from Causality, Shared Genetic Architecture and Transcriptomics

Rare Comorbidity between Inflammatory Bowel Disease and Primary Biliary Cholangitis: Evidence from Causality, Shared Genetic Architecture and Transcriptomics

Mendelian randomisation studies of Attention Deficit Hyperactivity Disorder

Investigating shared genetic architecture between obesity and multiple sclerosis

Contact Info

Product

Resources

About