北京大学学报（医学版）2024，Vol.56Issue(5)：775-780,6.DOI:10.19723/j.issn.1671-167X.2024.05.004
中国人群非综合征型唇裂伴或不伴腭裂的单核苷酸多态性遗传度
Single nucleotide polymorphism heritability of non-syndromic cleft lip with or without cleft palate in Chinese population
摘要
Abstract
Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.关键词
非综合征型唇裂伴或不伴腭裂/单核苷酸多态性遗传度/核心家系Key words
Non-syndromic cleft lip with or without cleft palate/Single nucleotide polymorphism heri-tability/Case-parent trios分类
医药卫生引用本文复制引用
薛恩慈,李静,周治波,朱洪平,吴涛,陈大方,胡永华,陈曦,王雪珩,王斯悦,王梦莹,李劲,秦雪英,武轶群,李楠..中国人群非综合征型唇裂伴或不伴腭裂的单核苷酸多态性遗传度[J].北京大学学报（医学版）,2024,56(5):775-780,6.基金项目
国家自然科学基金(81102178)Supported by the National Natural Science Foundation of China(81102178) （81102178）
