Dissecting the genetic overlap between severe mental disorders and markers of cellular aging: Identification of pleiotropic genes and druggable targets

Pisanu, Claudia; Congiu, Donatella; Meloni, Anna; Paribello, Pasquale; Patrinos, George P.; Severino, Giovanni; Ardau, Raffaella; Chillotti, Caterina; Manchia, Mirko; Squassina, Alessio

doi:10.1038/s41386-024-01822-5

Cited by 3 publications

(1 citation statement)

References 68 publications

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“…Recent advances in genomics statistical tools have unveiled the vital role of horizontal pleiotropy beyond vertical pleiotropy in shared genetic foundations across complex traits, as highlighted in a study by Gong et al 18 . However, prior research on horizontal pleiotropy has primarily concentrated on exploring the relationship between LTL and severe mental disorders 19 . Therefore, in light of the widespread associations reported in epidemiological studies and the existing evidence of a shared genetic basis LTL and CVDs, the necessity for a comprehensive, large-scale analysis is clear.…”

Section: Introductionmentioning

confidence: 99%

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

Qiao,

Wang,

Zhao

et al. 2024

Preprint

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Telomere shortening, a marker of cellular aging and genomic instability, has been epidemiologically linked to an increased risk of various cardiovascular diseases (CVDs). However, shared genetic determinants involved in these associations remain unclear. We composed an atlas of the shared genetic associations between leukocyte telomere length (LTL) and six major CVDs by investigating shared genetic elements, encompassing SNPs, genes, biological pathways, and protein targets with pleiotropic implications. Extensive genetic overlaps beyond genetic correlations were observed, but no causal relationships were established. We identified 248 independent pleiotropic genomic risk loci, implicating 50 unique genes in two or more trait pairs, especially theSH2B3gene, which was further validated by a proteome-wide Mendelian Randomization study. Functional analysis demonstrated a link to both DNA biosynthetic processes and telomere maintenance mechanisms. These findings suggest a genetic link between LTL and CVDs, highlighting a shared genetic basis crucial for developing future interventions and therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

Qiao,

Wang,

Zhao

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Contribution of leukocyte telomere length to major cardiovascular diseases onset: insights from a large-scale genome-wide cross-trait analysis

Pauklin,

Qiao,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

Telomere shortening, a marker of cellular aging and genomic instability, has been epidemiologically linked to an increased risk of various cardiovascular diseases (CVDs). However, shared genetic determinants involved in these associations remain unclear. We composed an atlas of the shared genetic associations between leukocyte telomere length (LTL) and six major CVDs by investigating shared genetic elements, encompassing SNPs, genes, biological pathways, and protein targets with pleiotropic implications. Extensive genetic overlaps beyond genetic correlations were observed, but no causal relationships were established. We identified 248 independent pleiotropic genomic risk loci, implicating 50 unique genes in two or more trait pairs, especially the SH2B3 gene, which was further validated by a proteome-wide Mendelian Randomization study. Functional analysis demonstrated a link to both DNA biosynthetic processes and telomere maintenance mechanisms. These findings suggest a genetic link between LTL and CVDs, highlighting a shared genetic basis crucial for developing future interventions and therapeutic targets.

show abstract

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

Pauklin,

Qiao,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

Telomere shortening, a marker of cellular aging and genomic instability, has been epidemiologically linked to an increased risk of various cardiovascular diseases (CVDs). However, shared genetic determinants involved in these associations remain unclear. We composed an atlas of the shared genetic associations between leukocyte telomere length (LTL) and six major CVDs by investigating shared genetic elements, encompassing SNPs, genes, biological pathways, and protein targets with pleiotropic implications. Extensive genetic overlaps beyond genetic correlations were observed, but no causal relationships were established. We identified 248 independent pleiotropic genomic risk loci, implicating 50 unique genes in two or more trait pairs, especially the SH2B3 gene, which was further validated by a proteome-wide Mendelian Randomization study. Functional analysis demonstrated a link to both DNA biosynthetic processes and telomere maintenance mechanisms. These findings suggest a genetic link between LTL and CVDs, highlighting a shared genetic basis crucial for developing future interventions and therapeutic targets.

show abstract

Dissecting the genetic overlap between severe mental disorders and markers of cellular aging: Identification of pleiotropic genes and druggable targets

Cited by 3 publications

References 68 publications

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

Contribution of leukocyte telomere length to major cardiovascular diseases onset: insights from a large-scale genome-wide cross-trait analysis

Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis

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