生物
表达数量性状基因座
全基因组关联研究
数量性状位点
遗传学
遗传关联
RNA剪接
遗传变异
基因
选择性拼接
计算生物学
基因型
单核苷酸多态性
核糖核酸
基因亚型
作者
Tingxiang Qi,Yang Wu,Hailing Fang,Fu-tao Zhang,Shouye Liu,Jian Zeng,Jian Yang
出处
期刊:Nature Genetics
[Springer Nature]
日期:2022-08-18
卷期号:54 (9): 1355-1363
被引量:54
标识
DOI:10.1038/s41588-022-01154-4
摘要
Most genetic variants identified from genome-wide association studies (GWAS) in humans are noncoding, indicating their role in gene regulation. Previous studies have shown considerable links of GWAS signals to expression quantitative trait loci (eQTLs) but the links to other genetic regulatory mechanisms, such as splicing QTLs (sQTLs), are underexplored. Here, we introduce an sQTL mapping method, testing for heterogeneity between isoform-eQTL effects (THISTLE), with improved power over competing methods. Applying THISTLE together with a complementary sQTL mapping strategy to brain transcriptomic (n = 2,865) and genotype data, we identified 12,794 genes with cis-sQTLs at P < 5 × 10-8, approximately 61% of which were distinct from eQTLs. Integrating the sQTL data into GWAS for 12 brain-related complex traits (including diseases), we identified 244 genes associated with the traits through cis-sQTLs, approximately 61% of which could not be discovered using the corresponding eQTL data. Our study demonstrates the distinct role of most sQTLs in the genetic regulation of transcription and complex trait variation.
科研通智能强力驱动
Strongly Powered by AbleSci AI