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- W4387142713 abstract "Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) remain unknown. Using the largest summary statistics of FTD (3,526 cases and 9,402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (rˆg=0.637, P=0.032) and identified 190 FTD-related variants within five loci (3p22.1, 5q35.1, 9p21.2, 19p13.11, and 20q13.13) using pleiotropy-informed methods. Among these, ALS and FTD had causal variants in 9p21.2 and 19p13.11. Moreover, MOBP (3p22.1), C9orf72 (9p21.2), MOB3B (9p21.2), UNC13A (19p13.11), SLC9A8 (20q13.13), SNAI1 (20q13.13), and SPATA2 (20q13.13) were discovered by both SNP- and gene-level analyses, which together discovered 15 FTD-associated loci and genes, with 10 not detected before (IFNK, RNF114, SLC9A8, SPATA2, SNAI1, SCFD1, POLDIP2, TMEM97, G2E3, and PIGW). Functional analyses showed these loci and genes were enriched in heart left ventricle, kidney cortex and some brain regions. Overall, this study provides insights into genetic determinants of FTD and shared genetic etiology underlying FTD and ALS." @default.
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- W4387142713 date "2023-09-01" @default.
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- W4387142713 title "Identifying risk loci for FTD and shared genetic component with ALS: a large-scale multi-trait association analysis" @default.
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- W4387142713 doi "https://doi.org/10.1016/j.neurobiolaging.2023.09.017" @default.
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