Study of Population-Differentiated Single-Nucleotide Variants in Human Immunoglobulin Loci Using Short-Read...

Population differences in immunoglobulin (IG) variation offer a starting point for studying inherited antibody diversity. We screened reference-based single-nucleotide variants for population differentiation and linked the resulting candidates to expression and trait annotations.

The primary analysis included 2488 participants from five 1000 Genomes Project groups after pruning documented pedigree relationships and incorporated reference-risk filtering, genotype-quality sensitivity, two FST estimators, linkage disequilibrium and resampling. A separate descriptive extension included 255 Simons Genome Diversity Project participants but did not constitute independent replication.

The four-estimate screening rule retained 231 conditional candidates: 49 in IGH and 182 in IGL, with none in IGK. Of these, 177 matched GTEx significant-eQTL catalogs, and seven coordinates overlapped 18 GWAS Catalog records. At rs2856876, the observed alternate-allele frequency was 70.04% in East Asian and 13.65% in European samples; annotations included an IGLV4-69 expression association and a protein-level trait with the same gene label. This correspondence identifies a question for molecular follow-up, not cross-assay validation. High-FST candidates were not consistently more likely to appear in GTEx catalogs than variants in supported local backgrounds. Local assembly-call disagreement, LD dependence and SGDP population composition further constrained interpretation.

The resource connects conditional population differences with specific expression and molecular-trait records for follow-up studies of antibody variation.