Expressive

rs1007000 (LPAR1): Gene Expression and Brain Imaging

Key takeaways

  • The alternative allele reduces LPAR1 expression in tibial artery and lung across 953 GTEx donors
  • The same allele also reduces MUSK, a neuromuscular signaling gene, in arterial and nerve tissue
  • A nearby gene shows increased activity in brain amygdala tissue when this allele is present
  • UK Biobank brain imaging studies with up to 40,000 participants have investigated the LPAR1 genomic region
  • The clinical significance of these expression changes has not been established in the provided studies

Key takeaways

  • rs1007000 is a variant near LPAR1 (Lysophosphatidic Acid Receptor 1), a gene active in arterial and lung tissue
  • The alternative allele reduces LPAR1 expression in tibial artery and lung, based on data from 953 GTEx donors
  • The same allele also reduces MUSK (Muscle Specific Kinase) expression in tibial artery and tibial nerve tissue
  • A nearby gene (ENSG00000301611) shows increased activity in brain amygdala tissue when this allele is present
  • Large-scale UK Biobank brain imaging studies with up to 40,000 participants have investigated this genomic region

What the research says GTEx data from 953 donors shows the alternative allele at rs1007000 reduces LPAR1 expression in tibial artery (slope -0.22, p=1.9e-10) and lung (slope -0.20, p=9.9e-8) GTEx Portal. The same allele reduces MUSK expression in tibial artery (slope -0.29, p=2.8e-10) and tibial nerve (slope -0.23, p=5.2e-7), and increases expression of ENSG00000301611 in brain amygdala (slope +0.39, p=1.4e-5) and cultured fibroblasts (slope +0.30, p=1.2e-12) GTEx Portal. UK Biobank brain imaging genome-wide association studies (GWAS) using samples of approximately 26,500 to nearly 40,000 participants have identified hundreds of genetic loci associated with regional brain structure and imaging phenotypes, with the LPAR1 genomic region among those examined.

Reported associations

  • LPAR1 expression, tibial artery: The alternative allele reduces LPAR1 expression (slope -0.22, p=1.9e-10, n=953 GTEx donors) GTEx Portal
  • LPAR1 expression, lung: The alternative allele reduces LPAR1 expression in lung tissue (slope -0.20, p=9.9e-8, n=953 GTEx donors) GTEx Portal
  • MUSK expression, tibial artery: The alternative allele reduces expression of MUSK in tibial artery (slope -0.29, p=2.8e-10) GTEx Portal
  • MUSK expression, tibial nerve: The alternative allele reduces MUSK expression in tibial nerve tissue (slope -0.23, p=5.2e-7) GTEx Portal
  • ENSG00000301611 expression, multiple tissues: The alternative allele increases expression of this gene in brain amygdala (slope +0.39, p=1.4e-5), esophageal mucosa (slope +0.35, p=2.8e-7), colon transverse (slope +0.34, p=7.1e-5), and cultured fibroblasts (slope +0.30, p=1.2e-12) GTEx Portal
  • Brain imaging phenotypes: A UK Biobank GWAS of approximately 3,935 brain imaging-derived phenotypes from nearly 40,000 participants identified 692 replicated variant-to-imaging associations; the LPAR1 region falls within the genomic scope of this analysis
  • Regional brain morphology: A multivariate GWAS (MOSTest) of 171 regional brain morphology measures from 26,502 UK Biobank participants identified 347 genomic loci, implicating more than 5% of all protein-coding genes

Evidence quality The expression QTL (eQTL) evidence from GTEx (953 donors, FDR<0.05) provides the most direct and statistically robust signal for rs1007000: the effect on ENSG00000301611 in cultured fibroblasts reaches p=1.2e-12, and the LPAR1 effect in tibial artery reaches p=1.9e-10, both clearing genome-wide significance thresholds. The brain imaging studies provide large-sample context (n=26,502 and n~40,000) but the study texts do not explicitly report per-SNP effect sizes for rs1007000 on individual brain imaging traits, so the magnitude of any brain-structural association is not determinable from the provided materials. No conflicting findings between the provided studies were identified. The evidence connecting LPAR1 expression changes in vascular or pulmonary tissue to specific clinical outcomes is preliminary, and the biological role of ENSG00000301611 in brain amygdala tissue is not established by the provided materials.

Tissue-specific expression effects

  • LPAR1: Reduced expression in tibial artery and lung; both effects clear p<1e-7 and represent decreased receptor gene activity in vascular and pulmonary tissue GTEx Portal
  • MUSK: Reduced expression in tibial artery and tibial nerve; effects reach p=2.8e-10 and p=5.2e-7 respectively, indicating decreased neuromuscular signaling gene activity in peripheral tissue GTEx Portal
  • ENSG00000301611: Increased expression in brain amygdala, esophageal mucosa, colon transverse, and cultured fibroblasts; the fibroblast effect is the most statistically robust at p=1.2e-12 GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does the LPAR1 gene do?

LPAR1 (Lysophosphatidic Acid Receptor 1) is a receptor gene expressed in arterial and lung tissue. GTEx data from 953 donors shows that the alternative allele at rs1007000 reduces its activity in both tissue types.

What traits is rs1007000 associated with?

rs1007000 is associated with reduced expression of LPAR1 in tibial artery and lung, and reduced expression of MUSK in arterial and nerve tissue. It has also been studied in large genome-wide brain imaging analyses using UK Biobank data.

Is rs1007000 linked to brain structure?

Large UK Biobank brain imaging studies have investigated the LPAR1 genomic region in samples of approximately 26,500 to 40,000 participants. GTEx data also shows this variant increases expression of a nearby gene in brain amygdala tissue, though the clinical relevance of this effect is not established by the available evidence.

What is MUSK and why does rs1007000 affect it?

MUSK (Muscle Specific Kinase) is a gene involved in neuromuscular signaling. GTEx data shows rs1007000 reduces MUSK expression in tibial artery (p=2.8e-10) and tibial nerve (p=5.2e-7), both reaching high statistical significance across 953 donors.

How strong is the evidence for rs1007000?

The expression QTL evidence from GTEx is statistically robust, with p-values reaching 1.2e-12 in cultured fibroblasts. Brain imaging associations come from studies with 26,000 to 40,000 participants, though specific per-SNP effect sizes for this variant on brain traits are not reported in the available study summaries.