Association between suicidal ideation and tandem repeats in contactins

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Background Death by suicide is one of the leading causes death among adolescents. Genome-wide association studies (GWAS) have identified loci that associate with suicidal ideation and related behaviours. One such group are six contactin genes ( CNTN1-6 ) critical to neurodevelopment through regulating neurite structure. Because single nucleotide polymorphisms (SNPs) detected GWAS often map non-coding intergenic regions, we investigated whether repetitive variants in CNTN s associated suicidality a young cohort aged 8 21. Understanding genetic liability thought behavior this age will promote early intervention treatment. Methods Genotypic phenotypic data were obtained from Philadelphia Neurodevelopment Cohort (PNC). Across s, 232 short tandem repeats (STRs) analyzed up 4,595 individuals European ancestry who expressed current, previous, or no ideation. STRs imputed into SNP arrays using phased SNP-STR haplotype reference panel 1000 Genomes Project. We tested several additive interactive models locus-level burden (i.e., sum STR alleles) respect Additive included sex, birth year, developmental stage (“DevStage”), first 10 principal components as covariates; assessed effect STR-by-DevStage considering all other covariates. Results CNTN1 -[T] N interacted DevStage increase risk for current -by-DevStage; p = 0.00035). Compared youngest group, middle (OR 1.80, 0.0514) oldest 3.82, 0.0002) participant groups had significantly higher odds their length expanded; result was independent polygenic scores Discussion These findings highlight diversity effects STR) acting on thoughts advance our understanding across childhood adolescence.

Language: Английский

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Multi-ancestry tandem repeat association study of hair colour using exome-wide sequencing

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 28, 2024

Abstract Hair colour variation is influenced by hundreds of positions across the human genome but this genetic contribution has only been narrowly explored. Genome-wide association studies identified single nucleotide polymorphisms (SNPs) influencing hair biology underlying these associations challenging to interpret. We report 16 tandem repeats (TRs) with effects on different models plus two TRs associated in diverse ancestry groups. Several expand or contract amino acid coding regions their localized protein such that structure, and extension function, may be altered. also demonstrate independent SNP variation, can used great an additive polygenic score predicts darker colour. This work adds growing body evidence regarding TR influence traits relatively large relative surrounding variation.

Language: Английский

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Correlations of the CNR1 Gene with Personality Traits in Women with Alcohol Use Disorder

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5174 - 5174

Published: May 9, 2024

Alcohol use disorder (AUD) is a significant issue affecting women, with severe consequences for society, the economy, and most importantly, health. Both personality alcohol disorders are phenotypically very complex, elucidating their shared heritability challenge medical genetics. Therefore, our study investigated correlations between microsatellite polymorphism (AAT)n of Cannabinoid Receptor 1 (CNR1) gene traits in women AUD. The group included 187 female subjects. Of these, 93 were diagnosed disorder, 94 controls. Repeat length regions CNR1 was identified PCR. All participants assessed Mini-International Neuropsychiatric Interview completed NEO Five-Factor State-Trait Anxiety Inventories. In AUD subjects, significantly fewer repeats present when compared controls (p = 0.0380). While comparing subjects controls, we observed higher scores on STAI trait < 0.00001) state scales 0.0001) Inventory Neuroticism Openness 0.0237; insignificant after Bonferroni correction) scales. Significantly lower results obtained NEO-FFI Extraversion 0.00003), Agreeability Conscientiousness by to There no statistically Pearson’s linear correlation number contrast, analysis showed positive scale (r 0.184; p 0.011; negative −0.241; 0.001). Interestingly, provided data two separate complex issues, i.e., (1) association females; (2) anxiety as non-alcohol dependent conclusion, plethora valuable improving understanding anxiety.

Language: Английский

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Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(7), P. e3002698 - e3002698

Published: July 1, 2024

The fitness effects of new mutations determine key properties evolutionary processes. Beneficial drive evolution, yet selection is also shaped by the frequency small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter trajectories outcomes in clonally evolving organisms such as viruses, microbes, tumors. small sizes these important have made accurate measurements their rates difficult. In assessing on growth be especially instructive, this complex phenotype closely linked to organisms. Here, we perform high-throughput time-lapse microscopy cells from mutation-accumulation strains precisely infer distribution mutational rate budding yeast, Saccharomyces cerevisiae . We show that are overwhelmingly negative, highly skewed towards very sizes, frequent enough suggest hitchhikers may impose a significant lineages. By using lines accumulated either wild-type or slippage repair-defective backgrounds, further disentangle 2 common types single-nucleotide substitutions simple sequence repeat indels, they distinct yeast rate. Although average mutation (approximately 0.3%), many do rate, implying class has an impact.

Language: Английский

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Polymorphic tandem repeats shape single-cell gene expression across the immune landscape

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Tandem repeats (TRs) – highly polymorphic, repetitive sequences dispersed across the human genome are crucial regulators of gene expression and diverse biological processes. Yet, due to historical challenges in their accurate calling analysis, TRs have remained underexplored compared single nucleotide variants (SNVs). Here, we introduce a cell type-specific resource exploring impact TR variation on expression. Leveraging whole single-cell RNA sequencing, catalog over 1.7 million polymorphic loci associations with more than 5 blood-derived cells from 1,790 individuals. We identify 58,000 quantitative trait (sc-eTRs), 16.6% which specific one 28 distinct immune types. Further fine-mapping uncovers 6,210 sc-eTRs as candidate causal drivers 21% genes tested genome-wide. show through colocalization that likely 2,000 GWAS associated immune-mediated hematological traits, further novel warranting investigation rare disease cohorts. pivotal, yet long-overlooked, contributors expression, promising implications for understanding pathogenesis genetic architecture complex traits.

Language: Английский

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