Expressive

rs11101314 (MAPK8): Adult Height Variant

Key takeaways

  • rs11101314, near the MAPK8 gene, was identified among 12,111 variants linked to adult height in a genome-wide study of 5,380,080 people
  • The alternate allele reduces MAPK8 expression specifically in the brain cerebellum and cerebellar hemisphere
  • Common SNPs from this study explain about 40-45% of height variation in European populations, but only 10-24% in other ancestries
  • Height-associated regions in this study span roughly 21% of the human genome across 7,209 segments
  • eQTL effects at this locus are tissue-specific, with brain and thyroid signals only

Key takeaways

  • rs11101314, near the MAPK8 gene, was identified as one of 12,111 variants linked to adult height in a genome-wide study of 5,380,080 people across five major ancestry groups
  • The alternate allele at this variant is associated with reduced MAPK8 expression specifically in brain regions, including the cerebellum and cerebellar hemisphere
  • Common SNPs from the height study collectively explain about 40-45% of height variation in European-ancestry populations, but only 10-24% in other ancestries
  • The height-associated genomic regions in this study span roughly 21% of the human genome across 7,209 segments
  • eQTL effects at this locus are tissue-specific, with brain and thyroid signals detected but no equivalent effects in other surveyed tissues

What the research says A genome-wide association meta-analysis of up to 5,380,080 individuals from 281 studies identified 12,111 independent SNPs significantly associated with adult height, clustered within 7,209 non-overlapping genomic segments with a mean size of roughly 90 kilobases and covering approximately 21% of the genome. These variants, including the MAPK8-region signal at rs11101314, collectively account for nearly all common-variant heritability of height, explaining roughly 40% of height variance in European-ancestry populations and 10-20% in other ancestries. In GTEx v11 data from 953 donors, the alternate allele is linked to reduced MAPK8 expression in the brain cerebellum (slope -0.39 log2 units, p=2.2e-5) and cerebellar hemisphere (slope -0.31 log2 units, p=1.4e-4), and to reduced AGAP12P expression in the thyroid (slope -0.50 log2 units, p=1.7e-4) GTEx Portal.

Reported associations

  • Adult height: identified as one of 12,111 genome-wide significant variants in a multi-ancestry GWAS of 5,380,080 individuals from 281 studies; no individual effect size is reported in the source material for this specific SNP
  • MAPK8 expression - brain cerebellum (eQTL): the alternate allele is associated with reduced expression (slope -0.39 log2 units, FDR<0.05) GTEx Portal
  • MAPK8 expression - brain cerebellar hemisphere (eQTL): the alternate allele is associated with reduced expression (slope -0.31 log2 units, FDR<0.05) GTEx Portal
  • AGAP12P expression - thyroid (eQTL): the alternate allele is associated with reduced expression (slope -0.50 log2 units, FDR<0.05) GTEx Portal

Evidence quality The height GWAS is among the largest human genetics studies conducted to date, with 5,380,080 participants from 281 cohorts spanning European (75.8%), East Asian (8.8%), Hispanic (8.5%), African (5.5%), and South Asian (1.4%) ancestry groups. The 12,111 identified SNPs reached conventional genome-wide significance thresholds and collectively account for nearly all of the common-SNP heritability of height. However, prediction accuracy for non-European populations is substantially lower, at roughly 10-24% of variance explained versus 40-45% in European populations, a gap the study attributes to differences in linkage disequilibrium patterns and allele frequencies across populations. No effect size specific to rs11101314 is reported in the provided study text. The GTEx eQTL data are from 953 donors and represent statistical associations between genotype and gene expression, not causal functional characterization. No conflicting findings on this variant are present in the source material.

Tissue-specific expression effects

  • MAPK8: the alternate allele is linked to reduced expression in the brain cerebellum (slope -0.39 log2 units, p=2.2e-5) and cerebellar hemisphere (slope -0.31 log2 units, p=1.4e-4); no equivalent signal was detected in other surveyed tissues GTEx Portal
  • AGAP12P: the alternate allele is linked to reduced expression in the thyroid (slope -0.50 log2 units, p=1.7e-4); no equivalent signal was detected in other surveyed tissues GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

Is rs11101314 linked to adult height?

Yes. rs11101314, located near the MAPK8 gene, was identified as one of 12,111 variants significantly associated with adult height in a large meta-analysis of 5,380,080 individuals from 281 studies across five major ancestry groups. Together, these variants collectively account for nearly all of the common-variant heritability of height.

What does rs11101314 do to MAPK8 gene expression?

According to GTEx v11 data from 953 donors, the alternate allele at rs11101314 is associated with reduced MAPK8 expression in two brain regions: the cerebellum and the cerebellar hemisphere. This effect appears to be tissue-specific, with no equivalent signal detected in other tissues surveyed.

What is an eQTL and why does it matter for rs11101314?

An eQTL (expression quantitative trait locus) is a genetic variant statistically associated with the expression level of a nearby gene in a specific tissue. For rs11101314, GTEx data show it acts as an eQTL for MAPK8 in the brain and for AGAP12P in the thyroid, meaning carrying the alternate allele is associated with lower gene expression in those tissues. eQTL effects describe a potential mechanism but do not establish disease risk on their own.

Does this variant affect height prediction equally across populations?

No. The height GWAS was conducted across five major ancestry groups, but prediction accuracy varies substantially. Common variants explain roughly 40-45% of height variation in European-ancestry populations, versus only about 10-24% in non-European populations. The study attributes this gap to differences in linkage disequilibrium and allele frequency patterns across populations.

Are there any known drug or disease effects associated with rs11101314?

The source material reviewed for this entry covers only height genetics and gene-expression associations. No drug response data or disease associations for rs11101314 are reported in the studies reviewed here.