Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributi...Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributions[1–3].The potential for shared genetic risk across related diseases has motivated us to examine the contributions of rare variants in canonical and non-canonical diseaseassociated genes in a group of MNDs to understand the gap in heritability.To this end,we have leveraged a wellcharacterized cohort from the CReATe(Clinical Research in amyotrophic lateral sclerosis and Related Disorders for Therapeutic Development)Consortium’s Phenotype-Genotype-Biomarker(PGB1)study.展开更多
基金The CReATe Consortium(U54 NS092091)is part of the NIH RDCRN,an initiative of the Office of Rare Diseases Research(ORDR),National Center for Advancing Translational Sciences(NCATS)CReATe is funded through a collaboration between NCATS and the National Institute of Neurologic Disorders and Stroke(NINDS)+1 种基金Supplemental support for the study included St.Jude Children’s Research Hospital American Lebanese Syrian Associated Charities(ALSAC)for genomics sequencing,and the ALS Association(grants 17-LGCA-331 and 16-TACL-242)for additional biorepository and sequencing supportThe analysis team is partly funded by National Cancer Institute grant P30 CA021765.MN is supported by the Wellcome Trust(226519/Z/22/Z).
文摘Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributions[1–3].The potential for shared genetic risk across related diseases has motivated us to examine the contributions of rare variants in canonical and non-canonical diseaseassociated genes in a group of MNDs to understand the gap in heritability.To this end,we have leveraged a wellcharacterized cohort from the CReATe(Clinical Research in amyotrophic lateral sclerosis and Related Disorders for Therapeutic Development)Consortium’s Phenotype-Genotype-Biomarker(PGB1)study.
