Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis

被引：1
作者：
Chen, Keying [1 ]
Gao, Tongyu [1 ]
Liu, Ying [1 ]
Zhu, Kexuan [1 ]
Wang, Ting [1 ]
Zeng, Ping [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构：
[1] Xuzhou Med Univ, Sch Publ Hlth, Dept Biostat, Xuzhou 221004, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Ctr Med Stat & Data Anal, Xuzhou 221004, Jiangsu, Peoples R China
[3] Xuzhou Med Univ, Key Lab Human Genet & Environm Med, Xuzhou 221004, Jiangsu, Peoples R China
[4] Xuzhou Med Univ, Key Lab Environm & Hlth, Xuzhou 221004, Jiangsu, Peoples R China
[5] Xuzhou Med Univ, Biol Data Min & Healthcare Transformat Innovat Eng, Xuzhou 221004, Jiangsu, Peoples R China
[6] Xuzhou Med Univ, Ctr Med Stat & Data Anal, Dept Biostat, Key Lab Human Genet & Environm Med,Key Lab Environ, Xuzhou 221004, Jiangsu, Peoples R China
[7] Xuzhou Med Univ, Biol Data Min & Healthcare Transformat Innovat Eng, Xuzhou 221004, Jiangsu, Peoples R China
来源：
NEUROBIOLOGY OF AGING | 2024年 / 134卷
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
Multitrait association analysis; Frontotemporal dementia; Amyotrophic lateral sclerosis; Genetic correlation; Pleiotropy; Summary statistics; Genome-wide association study; AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; FRONTOTEMPORAL DEMENTIA; HEXANUCLEOTIDE REPEAT; UNC13A; VARIANT; C9ORF72; ALZHEIMERS; DISEASE; TDP-43;
D O I：
10.1016/j.neurobiolaging.2023.09.017
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
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 (3526 cases and 9402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (r(g) = 0.637, P = 0.032) and identified 190 FTD-related variants within 5 loci (3p22.1, 5q35.1, 9p21.2, 19p13.11, and 20q13.13). 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 genes, with 10 not detected before (IFNK, RNF114, SLC9A8, SPATA2, SNAI1, SCFD1, POLDIP2, TMEM97, G2E3, and PIGW). Functional analyses showed these 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.
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收藏
页码：28 / 39
页数：12
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