rs117308259 (NUBPL): Immune Cell GWAS Variant

Key takeaways

• rs117308259, located near the NUBPL gene, was examined in a study that assessed roughly 22 million genetic variants against 731 immune cell traits in 3,757 Sardinians.
• The study detected 122 significant independent association signals (P < 1.28 x 10^-11) at 70 loci, 53 of which were novel, and 53 signals overlapped with known autoimmune disease risk loci.
• T cells and B cells show higher genetic heritability than innate immune cells, meaning inherited DNA plays a proportionally stronger role in shaping those lymphocyte levels.
• Specific effect sizes and directionality for this variant at the NUBPL locus are not reported in the available study excerpt; findings are preliminary.
• No lifestyle or drug-response data have been reported for this variant in the provided studies.

What the research says A genome-wide study in 3,757 Sardinians analyzed approximately 22 million variants for effects on 731 immune cell traits, including absolute cell counts, surface antigen expression levels, and morphological parameters, detecting 122 significant independent signals (P < 1.28 x 10^-11) for 459 traits at 70 loci, 53 of them newly identified. Fifty-three of those signals, drawn from 36 loci, overlapped with variants previously associated with disease, predominantly autoimmune disorders, suggesting these immune cell phenotypes may serve as intermediate steps in disease development. Narrow-sense heritability (the proportion of phenotypic variation explained by additive genetic effects) had a median of 37.0% across assessed traits, with lymphoid lineage cells such as naive T cells (47.0%) and naive B cells (44.7%) being more heritable than myeloid lineage cells (median 32.3%).

Reported associations

• Immune cell counts and proportions: The study identified associations with 459 distinct immune cell traits across 70 genetic loci, covering T cell, B cell, and myeloid subsets as well as ratios between cell types.
• Surface antigen expression levels: Median fluorescence intensity values (reflecting how much of a given cell-surface protein is present on each cell) were among the traits significantly associated at detected loci.
• Autoimmune disease overlap: Fifty-three signals overlapped with previously reported autoimmune disease risk variants, pointing to specific immune cell subtypes as potential mediators of autoimmune pathogenesis.

Evidence quality The sole available study (Orru V et al., Nature Genetics, 2020) analyzed 3,757 individuals from a founder Sardinian population using approximately 22 million variants derived from population-specific whole-genome sequencing, and applied a significance threshold of P < 1.28 x 10^-11, which is substantially more stringent than the standard GWAS threshold of P < 5 x 10^-8, increasing confidence in signals detected across the study as a whole. Sardinia is a genetic isolate, and generalizability to non-Sardinian populations has not been demonstrated in the provided text. Specific effect sizes, confidence intervals, and independent replication data for the NUBPL locus individually are not provided in the available excerpt. Evidence for this variant's specific associations should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.