What question did this study set out to answer?

To determine the prevalence of known ALS-associated genetic variants and evaluate whether oligogenic or polygenic risk architectures influence clinical features in sporadic ALS.

May 14, 2020Journal of Medical Genetics

Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis

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Authors

EMEmily P. McCannMacquarie University LHLyndal HendenMacquarie University JFJennifer A. FifitaThe University of Sydney

Discussion

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Implication

Genomic cohort study reveals multiple disease-linked mutations in sporadic amyotrophic lateral sclerosis, highlighting an oligogenic architecture that drives earlier disease onset.

Key Points

To determine the prevalence of known ALS-associated genetic variants and evaluate whether oligogenic or polygenic risk architectures influence clinical features in sporadic ALS.
Analyzed clinical data (n=567) and whole-genome sequencing (WGS) data (n=616) from a cohort of 757 sporadic ALS cases recruited from Australian neurology clinics, with 426 cases having both datasets.
Interrogated WGS data for 853 previously reported ALS-linked mutations or risk alleles across more than 30 genes.
Evaluated cryptic relatedness between variant carriers using identity-by-descent analysis and tested correlations between variant burden and age of disease onset.
Identified 43 ALS-implicated variants across 18 genes (including C9orf72, ATXN2, TARDBP, SOD1, SQSTM1, and SETX), with 33.3% of sporadic cases harboring at least one variant and 6.82% carrying two or more.
Cases carrying multiple ALS-linked variants (oligogenic/polygenic burden) exhibited a significantly earlier age of onset compared to individuals carrying no reported variants.
Detected cryptic relatedness via identity-by-descent in sporadic pairs sharing identical rare variants, including SOD1 p.I114T (two cases) and SQSTM1 p.K238E (three cases).

Cite This Study

McCann et al. (2020) studied this question.

synapsesocial.com/papers/6a9635306fef75547198894d https://doi.org/10.1136/jmedgenet-2020-106866

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May 14, 2020Journal of Medical Genetics

Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis

View Full Paper

Ask AI

Bookmark

Authors

EMEmily P. McCannMacquarie University LHLyndal HendenMacquarie University JFJennifer A. FifitaThe University of Sydney

Discussion

Member takes

Implication

Genomic cohort study reveals multiple disease-linked mutations in sporadic amyotrophic lateral sclerosis, highlighting an oligogenic architecture that drives earlier disease onset.

Key Points

To determine the prevalence of known ALS-associated genetic variants and evaluate whether oligogenic or polygenic risk architectures influence clinical features in sporadic ALS.
Analyzed clinical data (n=567) and whole-genome sequencing (WGS) data (n=616) from a cohort of 757 sporadic ALS cases recruited from Australian neurology clinics, with 426 cases having both datasets.
Interrogated WGS data for 853 previously reported ALS-linked mutations or risk alleles across more than 30 genes.
Evaluated cryptic relatedness between variant carriers using identity-by-descent analysis and tested correlations between variant burden and age of disease onset.
Identified 43 ALS-implicated variants across 18 genes (including C9orf72, ATXN2, TARDBP, SOD1, SQSTM1, and SETX), with 33.3% of sporadic cases harboring at least one variant and 6.82% carrying two or more.
Cases carrying multiple ALS-linked variants (oligogenic/polygenic burden) exhibited a significantly earlier age of onset compared to individuals carrying no reported variants.
Detected cryptic relatedness via identity-by-descent in sporadic pairs sharing identical rare variants, including SOD1 p.I114T (two cases) and SQSTM1 p.K238E (three cases).

Cite This Study

McCann et al. (2020) studied this question.

synapsesocial.com/papers/6a9635306fef75547198894d https://doi.org/10.1136/jmedgenet-2020-106866

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