Expressive

rs11250130 (TDH): Speech Rhythm and Muscle Mass

Key takeaways

  • rs11250130 near TDH showed a suggestive (below genome-wide significance) link to speech rhythm perception in a GWAS of 1,501 people.
  • A large GWAS of over 85,000 UK Biobank participants linked this region to appendicular lean mass (arm and leg muscle), replicated in 181,000+ elderly individuals.
  • GTEx data shows this variant increases expression of TDH-AS1 in multiple brain regions including the frontal cortex and hippocampus.
  • The variant reduces FAM167A-AS1 expression in skeletal muscle, providing a potential biological link to muscle mass findings.
  • All evidence is preliminary; the prosody signal especially needs replication in larger samples before firm conclusions can be drawn.

Key takeaways

  • rs11250130, near the TDH gene, showed a suggestive (below genome-wide significance) association with speech rhythm perception in a genome-wide study of 1,501 individuals.
  • A large GWAS linked this genomic region to appendicular lean mass (combined arm and leg muscle) in over 85,000 UK Biobank participants, with replication in 181,862 elderly individuals.
  • GTEx data shows the variant increases expression of TDH-AS1 in several brain regions including the frontal cortex and hippocampus, as well as in the pancreas.
  • The variant reduces FAM167A-AS1 expression in skeletal muscle, spanning a tissue expression profile that includes the nervous system, pancreas, and musculoskeletal system.
  • All findings are preliminary; the prosody association in particular needs replication in larger samples before firm conclusions can be drawn.

What the research says A GWAS of prosody (speech rhythm) perception in 1,501 participants yielded 14 suggestive signals (p < 5.00 x 10^-6), with rs11250130 among the reported loci; cross-trait analyses in the same study found shared genetic architecture between prosody perception, word reading, and musical beat synchronization. A separate large-scale GWAS identified 182 loci associated with appendicular lean mass (ALM) at genome-wide significance in 85,750 middle-aged UK Biobank participants, replicated in 181,862 elderly individuals from the same biobank, with in vitro follow-up identifying CPNE1 and STC2 as modifiers of myogenesis (the process by which muscle cells form).

Reported associations

  • Prosody (speech rhythm) perception: Suggestive association (p < 5.00 x 10^-6) with scores on the Test of Prosody via Syllable Emphasis (TOPsy), a measure of sensitivity to stress patterns in spoken language; n = 1,501.
  • Appendicular lean mass: Association with total arm and leg skeletal muscle mass in a GWAS of 85,750 middle-aged adults, replicated in 181,862 elderly individuals.

Evidence quality The prosody GWAS is small by GWAS standards (n = 1,501) and signals at this locus reached only suggestive significance (p < 5 x 10^-6), falling short of the conventional genome-wide significance threshold (p < 5 x 10^-8). No independent replication cohort was described for the specific prosody finding. The appendicular lean mass GWAS is substantially larger and better powered (n = 85,750 discovery, n = 181,862 replication), with associations evaluated at genome-wide significance. The two traits involved (prosody perception and muscle mass) are biologically distinct, and whether the same causal variant underlies both signals remains to be confirmed through further investigation. Overall, evidence for this specific variant is preliminary to moderate, with the muscle mass literature better supported than the prosody finding.

Tissue-specific expression effects

  • TDH-AS1 (a long non-coding RNA antisense to TDH): The alternate allele is linked to increased expression in the pancreas, frontal cortex (Brodmann area 9), hippocampus, nucleus accumbens (basal ganglia), and stomach GTEx Portal.
  • TDH (threonine dehydratase homolog): The alternate allele is linked to increased expression in the pancreas GTEx Portal.
  • ENSG00000269954: The alternate allele is linked to reduced expression in cultured fibroblasts GTEx Portal.
  • FAM167A-AS1 (a long non-coding RNA): The alternate allele is linked to reduced expression in skeletal muscle GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the TDH gene?

TDH encodes threonine dehydratase homolog, an enzyme involved in amino acid processing. The nearby non-coding RNA TDH-AS1 shows altered expression linked to rs11250130 in brain tissue, the pancreas, and stomach according to GTEx data.

Is rs11250130 linked to speech or reading ability?

A genome-wide study found a suggestive association between rs11250130 and prosody (speech rhythm) perception, which plays a role in reading and language comprehension. However, the signal did not reach the standard genome-wide significance threshold, so findings are preliminary and require replication.

Does rs11250130 affect muscle mass?

A large genome-wide study of over 85,000 UK Biobank participants found associations at this genomic region with appendicular lean mass (arm and leg muscle), replicated in a second cohort of 181,000+ elderly individuals. This evidence is better powered than the prosody finding.

Which tissues does rs11250130 affect at the gene expression level?

GTEx data links this variant to increased TDH-AS1 expression in the pancreas, frontal cortex, hippocampus, nucleus accumbens, and stomach, and to increased TDH expression in the pancreas. It also links to reduced FAM167A-AS1 expression in skeletal muscle and reduced ENSG00000269954 expression in cultured fibroblasts.

How strong is the evidence for rs11250130?

Evidence is mixed. The muscle mass GWAS is large (85,000+ discovery, 181,000+ replication) and used genome-wide significance thresholds. The prosody perception GWAS is smaller (n = 1,501) and reported only suggestive significance, so replication in larger samples is needed before drawing firm conclusions.