rs11991223 (ADAM7-AS1): Height-Associated Variant

Key takeaways

• Identified in the largest-ever height genetics study, covering roughly 5.4 million people worldwide
• Located within ADAM7-AS1, a noncoding RNA gene that does not directly make a protein
• The alternate allele reduces ADAM28 gene activity in stomach and colon tissue, suggesting a regulatory role
• Height predictions based on all 12,111 similar variants work best in European-ancestry populations and are less reliable in other groups
• No specific effect size for this variant alone is available in the provided study text

What the research says rs11991223 is located within ADAM7-AS1, a long noncoding antisense RNA gene (meaning it produces an RNA molecule that is complementary to a nearby gene and may help regulate its activity), and was identified among 12,111 independent single-nucleotide polymorphisms (SNPs, single-letter changes in DNA sequence) significantly associated with adult height in a large genome-wide association study (GWAS) of approximately 5.4 million individuals spanning five major ancestry groups. The study found that these variants collectively account for roughly 40% of height variation in European-ancestry populations and around 10-20% in populations of other ancestries, with reduced prediction accuracy attributed to differences in linkage disequilibrium (the tendency for nearby genetic variants to be inherited together) and allele frequencies across groups. Separately, GTEx expression data show that the alternate allele at this locus is linked to reduced expression of the nearby gene ADAM28 in stomach and transverse colon tissue GTEx Portal.

Reported associations

• Adult height: Identified as one of 12,111 genome-wide significant common SNPs in a GWAS of approximately 5.4 million individuals; the full set of identified variants together explains roughly 40% of height variance in European-ancestry populations and 10-20% in other ancestry groups

Evidence quality The height association rests on a large discovery sample of approximately 5.4 million individuals from 281 contributing studies, spanning European (75.8%), East Asian (8.8%), Hispanic (8.5%), African (5.5%), and South Asian (1.4%) ancestry groups. The study identified 12,111 independent genome-wide significant SNPs covering approximately 21% of the genome across 7,209 non-overlapping genomic segments, representing the most comprehensive common-variant height map published to date. Specific per-SNP effect sizes and p-values for rs11991223 are not reported in the provided study text, so the individual strength of association for this variant cannot be independently assessed from available materials. Prediction accuracy is substantially lower in non-European populations, and the study authors note that further research is needed to achieve equivalent coverage in other ancestries. No conflicting findings for this specific variant are noted in the available materials.

Tissue-specific expression effects

• ADAM28: The alternate allele is associated with reduced expression in stomach tissue and in transverse colon tissue, based on cis-eQTL data from 953 donors GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.