PubMed HealthSearch

Biomedical subjects

Gabriel R Fries

Publications and source records attributed to Gabriel R Fries.

3 recordsLinked to original sources

Suicidality phenotypes reflect both shared and distinct genetic factors.

Suicidality phenotypes, including suicidal ideation (SI), non-fatal suicide attempt (SA), and suicide death (SD), are heritable and exhibit both shared and phenotype-specific genetic influences. Using genomic structural equation modelling, we estimated the shared genetic architecture across GWAS of SI (176,147 cases, 1,010,300 controls), SA (53,919 cases, 1,063,988 controls), and SD (7,584 cases, 652,070 controls) and conducted a multivariate GWAS of a latent suicidality factor capturing their shared liability. This analysis identified 36 genome-wide significant loci, including seven not previously reported in any suicidality GWAS. Follow-up analyses identified residual genetic variance specific to each phenotype, including three SD-specific genomic risk loci. Conditioning suicidality phenotypes on genetic liability to psychiatric disorders revealed significant residual genetic variance across SI, SA, SD, and the suicidality common factor. Together, these results suggest that suicidality reflects both shared genetic liability and phenotype-specific contributions.

Journal Article

Optimizing genetic ancestry adjustment in DNA methylation studies: a comparative analysis of approaches.

BACKGROUND: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry. METHODS: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control probe PCs, sex, age, and cell type proportions to remove the effects of technical and biological factors, and (2) integrating the residualized data with genotype calls from the SNP probes (commonly referred to as rs probes) present on the arrays, before calculating PCs and evaluated the clustering ability and relationship to genetic ancestry. RESULTS: The PCs generated by EpiAnceR+ led to improved clustering for repeated samples from the same individual and stronger associations with genetic ancestry groups predicted from genotype information compared to the original approach. EpiAnceR+ also outperformed the use of DNA methylation PCs or surrogate variables for ancestry adjustment. CONCLUSIONS: We show that the EpiAnceR+ approach improves the adjustment for genetic ancestry in DNA methylation studies. EpiAnceR+ can be integrated into existing R pipelines for commercial methylation arrays, such as 450 K, EPIC v1, and EPIC v2. The code is available on GitHub ( https://github.com/KiraHoeffler/EpiAnceR ).

DNA Methylation

The landscape of suicide risk factors in Latin America.

Suicide is a leading cause of death globally, with over 75 % of cases occurring in low- and middle-income countries (LMICs). Latin America, a severely underrepresented region in suicide research, has experienced a 6 % increase in its suicide rate from 2010 to 2016, contrasting with a global decline. In this commentary, we provide an overview of the epidemiological, social, and clinical factors influencing suicide in Latin America. We highlight the distinct trends in Latin America compared to other world regions, including the significant disparities in mental health care accessibility. Our review also considers the role of sociocultural factors such as strong family ties, traditional gender norms, and the impact of religiosity on stigma and care-seeking behaviors. Additionally, we address the lack of representation of Latin American populations in genetic studies on suicide, which hinders the identification of relevant biological markers and the development of tailored interventions. We call for increased research on the clinical, genetic, and social determinants of suicide in this region to better understand risk factors and ultimately inform suicide prevention strategies. Addressing this gap is critical for reducing suicide rates in Latin America.

Humans