rs11016281 (LINC01163): Gut Microbiome Diversity

Key takeaways

• rs11016281 sits in the LINC01163 - LINC02667 region at chromosome 10p15.1, one of only five genetic loci significantly linked to gut microbiome diversity in a large Japanese genome-wide study.
• The five identified loci together explain only a small fraction of microbiota variation, pointing to a highly polygenic genetic architecture (meaning the trait is shaped by many variants with small effects rather than a few large ones).
• The study enrolled 1068 healthy Japanese adults and adjusted for 138 lifestyle and demographic factors to isolate genetic contributions.
• Evidence is preliminary: a single study conducted in one ancestry group with no independent replication reported.
• GTEx expression data show the ALT allele is associated with increased expression of a nearby gene in testis tissue, though the functional significance of this is not established.

What the research says A genome-wide association study (GWAS - a method that scans hundreds of thousands of genetic variants across a large group to find those statistically tied to a trait) in 1068 healthy Japanese adults identified the chromosomal region 10p15.1, where LINC01163 and LINC02667 reside, as one of five loci significantly associated with gut microbiome diversity measures PMID 34385598. The analysis incorporated 138 extrinsic and demographic variables as covariates to reduce confounding from factors such as diet, medication, and physical activity PMID 34385598. Despite these genome-wide significant hits, all five loci together account for only a small fraction of microbiota variation, leading the authors to conclude that gut microbiota composition is governed by a highly polygenic architecture PMID 34385598.

Reported associations

• Gut microbiome diversity: The 10p15.1 locus (LINC01163 - LINC02667 region) was one of five loci reaching genome-wide significance for microbiome diversity measures in 1068 healthy Japanese adults; the specific diversity metric associated with this locus is not detailed in the available text, and the five significant loci together explain only a small fraction of total microbiota variation PMID 34385598.

Evidence quality Evidence rests on a single study of 1068 Japanese adults that used 16S rRNA gene sequencing (a technique that identifies bacterial communities by sequencing a conserved region of a bacterial gene) to profile the gut microbiota, while incorporating 138 covariates to reduce confounding PMID 34385598. The 10p15.1 locus reached genome-wide significance, but the specific p-value and effect size for rs11016281 individually are not reported in the available text. The Japanese-only sample is both an asset (the population's genetic homogeneity reduces spurious associations arising from population stratification) and a limitation (generalizability to other ancestries is unknown). No replication in an independent cohort is described. Overall, evidence for this variant should be considered preliminary.

Tissue-specific expression effects

• ENSG00000289087: Carriers of the ALT allele show increased expression of this gene specifically in testis tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.