Study of Population-Differentiated Single-Nucleotide Variants in Human Immunoglobulin Loci Using Short-Read Sequencing Data.
- 1Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
Abstract
Background/objectives
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.Methods
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.Results
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.Conclusions
The resource connects conditional population differences with specific expression and molecular-trait records for follow-up studies of antibody variation.
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BibTeX
@article{zhang2026study,
title = {{Study of Population-Differentiated Single-Nucleotide Variants in Human Immunoglobulin Loci Using Short-Read Sequencing Data.}},
author = {Qi Zhang and Xudong Chen and Qiang Li},
journal = {Genes},
year = {2026},
month = sep,
doi = {10.3390/genes17101216},
url = {https://europepmc.org/article/MED/42938332},
note = {CC BY},
}
RIS
TY - JOUR
TI - Study of Population-Differentiated Single-Nucleotide Variants in Human Immunoglobulin Loci Using Short-Read Sequencing Data.
AU - Qi Zhang
AU - Xudong Chen
AU - Qiang Li
PY - 2026
DA - 2026/09/30
JO - Genes
DO - 10.3390/genes17101216
UR - https://europepmc.org/article/MED/42938332
AB - Background/objectives 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.Methods 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.Results 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.Conclusions The resource connects conditional population differences with specific expression and molecular-trait records for follow-up studies of antibody variation.
SN - 2073-4425
ER -