rs11107078 (SOCS2-AS1): Height and MRPL42 Expression

Key takeaways

• This variant in the SOCS2-AS1 locus (antisense RNA 1 adjacent to the SOCS2 gene) was among 12,111 SNPs identified in the largest genome-wide height study to date, which enrolled 5.4 million participants from diverse ancestries.
• Those 12,111 variants together explain roughly 40% of height variation in people of European ancestry, or about 45% when all common variants in the HapMap 3 panel are included.
• The alternate allele at this position is linked to lower MRPL42 gene activity in aortic and tibial arteries, the gastroesophageal junction, and subcutaneous fat.
• Height prediction from these variants is substantially less accurate in non-European populations, a recognized gap in current genetic research.

What the research says A genome-wide association study of 5.4 million individuals from 281 studies identified 12,111 independent SNPs significantly associated with adult height, clustering within roughly 7,200 genomic segments that together cover about 21% of the genome; these variants account for approximately 40% of height-related phenotypic variance in European-ancestry populations, or about 45% when all HapMap 3 panel SNPs are included. Prediction accuracy drops to approximately 10-20% in non-European populations, partly due to differences in linkage disequilibrium (the statistical tendency for nearby variants to be co-inherited) and allele frequency across ancestry groups, though effect sizes and associated regions are described as broadly consistent across ancestries. GTEx v11 data (953 donors, FDR < 0.05) show the alternate allele at rs11107078 is also an eQTL (expression quantitative trait locus - a variant that influences how much a gene is produced) for MRPL42, reducing its expression in aortic and tibial arteries, the gastroesophageal junction, and subcutaneous adipose tissue GTEx Portal.

Reported associations

• Human height: rs11107078 was identified among 12,111 height-associated SNPs in a GWAS of 5.4 million individuals; those variants collectively account for approximately 40% of phenotypic variance in European-ancestry populations and roughly 10-20% in non-European groups.
• MRPL42 expression (multiple tissues): The alternate allele is associated with reduced MRPL42 expression in aortic artery, tibial artery, the gastroesophageal junction, and subcutaneous adipose tissue GTEx Portal.

Evidence quality The height association comes from the largest GWAS of this trait published to date, with 5.4 million participants across 281 studies; approximately 76% were of European ancestry, with the remainder drawn from East Asian (approximately 9%), Hispanic (approximately 8%), African (approximately 5.5%), and South Asian (approximately 1.4%) groups. The 12,111 identified SNPs are described as accounting for nearly all common SNP-based heritability of height in European-ancestry populations, and the associated genomic map is characterized as largely saturated for that ancestry group, meaning additional common variants of meaningful effect are unlikely to be discovered with larger European samples. The study explicitly acknowledges that substantially lower prediction accuracy in non-European populations represents an unresolved limitation. The MRPL42 eQTL data derive from GTEx v11 (953 donors, FDR < 0.05) and reflect tissue-level gene-expression associations; they do not by themselves establish a causal pathway linking this locus to height or any clinical outcome GTEx Portal.

Tissue-specific expression effects

• MRPL42: The alternate allele at rs11107078 is associated with reduced expression of this mitochondrial ribosomal protein gene across four tissues, with the largest reduction in aortic artery, followed by the gastroesophageal junction, subcutaneous adipose, and tibial artery GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.