In this study, we investigated the association between 5 interferon regulatory factor-5 (IRF5) single nucleotide polymorphisms (SNPs) and autoimmune diseases using the Medline citation index. Twenty-eight studies with 74 comparisons, including 16 rheumatoid arthritis (RA), 43 systemic lupus erythematous (SLE), 2 juvenile idiopathic arthritis (JIA), 6 multiple sclerosis (MS), and 5 systemic sclerosis (SSc) studies, were examined in the meta-analysis. The SNP rs2004640 was significantly associated with SLE, MS, and SSc, but not with JIA [odds ratio (OR)=1.06, 95% confidence interval (CI)=0.90-1.24, P=0.48] or RA (OR=1.03, 95%CI=0.95-1.11, P=0.44). A significant association was observed between rs2280714 and SLE, MS, and SSc, but not RA (OR=1.01, 95%CI=0.94-1.09, P=0.80). Rs10954213 was associated with the pathogenesis of SLE, RA, MS, and SSc. rs2070197 and the exon 6 insertion were significantly associated with SLE. Haplotypes containing rs2004640T and rs2280714T were significantly associated with an increased risk of SLE, but not with RA. This meta-analysis certified that IRF5 polymorphisms confer susceptibility to SLE, MS, and SSc. To further confirm the correlations between polymorphisms of IRF5 and autoimmune disease susceptibility, studies involving a larger number of patients worldwide are necessary.

The revolution in large-scale human genomics and advancements in statistical methods have profoundly refined our understanding of genetic diversity and structure within human populations. Y-chromosome variations, with their distinct evolutionary characteristics, play crucial roles in reconstructing the origins and interactions of ancient East Asian paternal lineages. We launched the YanHuang cohort employing a high-resolution capture sequencing panel to explore the evolutionary trajectory of Han Chinese, one of the world’s largest ethnic groups. We generated paternal genomic data for 5020 Han Chinese individuals across 29 Chinese administrative regions. We observed that multiple founding paternal lineages originating from ancient western Eurasia, Siberia, and East Asia contributed significantly to the Han Chinese gene pool. We identified fine-scale paternal genetic structures shaped by interactions among ancient populations and geographic barriers like the Qinling-Huaihe line and the Nanling Mountains. These structures reflect both isolation-enhanced and admixture-driven genetic differentiation, underscoring the complexity of Han Chinese genomic diversity. We observed a strong correlation between the frequency of multiple founding lineages and subsistence-related ancestral sources, including western pastoralists, Holocene Mongolian Plateau populations, and ancient East Asians. This relationship highlights the impact of ancient migrations and admixture on Chinese paternal genomic diversity. We introduced the Weakly-Differentiated Multi-Source Admixture model to clarify the intricate interactions among multiple ancestral sources influencing the Han Chinese paternal landscape. This study provides a comprehensive uniparental genomic resource from the YanHuang cohort, proposes a novel admixture model, and delineates the complex genomic landscape shaped by ancient herders, hunter-gatherers, and farmers integral to Han Chinese ancestry.