Expressive

rs117991621 (HAL): Metabolomics Variant

Key takeaways

  • rs117991621 is a variant in the HAL gene, identified in an exome-wide metabolomics study of an Alpine population cohort.
  • The study tested 175 metabolites in 5505 participants and found 85 significant associations, 39 of them previously unreported.
  • Some variants in this cohort were over five times more common than in other European populations, pointing to possible population-specific effects.
  • Evidence for this variant is preliminary, coming from a single exploratory study without documented independent replication.

Key takeaways

  • rs117991621 is a genetic variant in the HAL gene, identified in an exome-wide study of blood metabolite levels in an Alpine population cohort.
  • The study that surfaced this variant tested 175 metabolites in 5505 participants and found 85 significant coding-variant associations, 39 of which were novel.
  • Some variants in the study cohort were more than five times more common than in other European populations, suggesting population-specific effects in this Alpine community.
  • Evidence for this specific variant is from a single exploratory cohort study without documented independent replication and should be considered preliminary.

What the research says An exome-wide association study (ExWAS) - a genetic scan restricted to protein-coding regions of the genome - of 175 metabolites in 5505 participants of the Cooperative Health Research in South Tyrol (CHRIS) study, a population-based longitudinal cohort in North Italy, identified 85 significant single-variant associations across 40 metabolites, of which 39 were previously unreported. Fifteen associations involved variants more than five times more common in the cohort than in non-Finnish Europeans in the gnomAD reference database, suggesting some findings reflect population-specific genetic architecture in this Alpine community. The variant rs117991621 resides in the HAL gene; specific details about its associated metabolite trait, effect size, and statistical significance are not available in the excerpts of the source study provided here.

Reported associations

  • Metabolite levels (CHRIS ExWAS): Identified among 85 significant variant-metabolite associations in an exome-wide scan of 175 metabolites in 5505 participants; the specific metabolite linked to rs117991621 is not described in the available study excerpts.

Evidence quality The source study (Konig et al., Metabolites, 2023) enrolled 5505 CHRIS participants, combining whole-exome sequencing of 3294 individuals with imputation into 2211 additional participants. Imputation quality was high, with a mean squared correlation of 0.913 and a median of 0.978 between imputed dosages and sequencing hard calls; rare variants with a minor allele count between 2 and 10 in the reference panel achieved a mean squared correlation of 0.96. The design is exploratory and single-cohort; no independent replication of rs117991621 is documented in the provided materials. A second provided study (Richardson et al., PLoS Biology, 2022) evaluated genetically predicted effects of lipid-modifying drug targets - including HMGCR, PCSK9, CETP, and others - on the blood metabolome in up to 115,082 UK Biobank participants, but does not report findings relevant to the HAL locus based on the available text. Evidence for rs117991621 should be considered preliminary, pending replication in independent cohorts.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs117991621?

rs117991621 is a genetic variant in the HAL gene. It was identified in an exome-wide association study of blood metabolite levels in a population cohort from South Tyrol, Italy.

Which study identified rs117991621?

The variant emerged from the Cooperative Health Research in South Tyrol (CHRIS) study, which scanned protein-coding variants across the genome to find associations with 175 blood metabolites in 5505 participants.

Is the evidence for rs117991621 well-established?

Not yet. The evidence is from a single exploratory cohort study, and independent replication in other populations has not been documented in the available literature. Findings should be treated as preliminary.

Is rs117991621 a rare variant?

The source study covered both common and rare coding variants. Some variants it found were more than five times more common in this Alpine cohort than in other Europeans, but the exact frequency of rs117991621 is not stated in the available text.

What metabolite is rs117991621 associated with?

The specific metabolite linked to rs117991621 in the HAL gene is not described in the excerpts of the source study available here. The broader study identified 85 metabolite associations across 40 different metabolites.