rs1049970 (CDH5): Cardiometabolic Protein QTL
Key takeaways
- rs1049970 was identified as a pQTL for CDH5 in a whole-genome sequencing study of 248 cardiometabolic serum proteins across 2,893 individuals
- 58.8% of pQTLs in the study replicated in an independent cohort from the Orkney Islands
- This variant increases LINC00920 expression in brain and nerve tissue but decreases it in whole blood
- Evidence is from isolated Greek population cohorts; broader ancestry generalizability is not established
- GTEx data across 953 donors confirms the LINC00920 eQTL effect with highly significant p-values
Key takeaways
- rs1049970 was identified as a pQTL for CDH5 in a whole-genome sequencing study of 248 cardiometabolic serum proteins across 2,893 individuals
- 58.8% of pQTLs in the study replicated in an independent cohort from the Orkney Islands
- This variant increases LINC00920 expression in brain and nerve tissue but decreases it in whole blood
- Evidence is from isolated Greek population cohorts; broader ancestry generalizability is not established
- GTEx data across 953 donors confirms the LINC00920 eQTL effect with highly significant p-values
What the research says A whole-genome sequencing pQTL analysis of 248 cardiometabolic-relevant serum proteins in 2,893 individuals from two isolated Greek cohorts (MANOLIS, n=1,356; Pomak, n=1,537) identified rs1049970 as associated with CDH5 protein levels. The study detected 301 independently associated pQTLs (P < 7.45 x 10^-11) for 170 proteins overall, with 58.8% replicating in the independent ORCADES cohort from the Orkney Islands. Separately, GTEx data show this variant increases LINC00920 expression in multiple neural and peripheral tissues while decreasing it in whole blood GTEx Portal.
Reported associations
- CDH5 serum protein levels: rs1049970 was identified as a pQTL for CDH5 in a study of 248 cardiometabolic proteins involving 2,893 individuals from two isolated Greek cohorts; a specific effect size for this variant-protein pair was not available in the provided study text
- LINC00920 expression in neural and peripheral tissue (increased): the alternate allele is associated with increased LINC00920 expression in cervical spinal cord (slope +1.05, p=2.3e-38), testis (+0.92, p=1.6e-78), hippocampus (+0.82, p=8.5e-31), putamen basal ganglia (+0.81, p=6.7e-28), tibial nerve (+0.75, p=2.5e-86), sun-exposed lower leg skin (+0.63, p=2.4e-56), and non-sun-exposed skin (+0.62, p=7.3e-48) GTEx Portal
- LINC00920 expression in whole blood (decreased): the alternate allele is associated with decreased LINC00920 expression in whole blood (slope -0.57, p=2.6e-48), in the opposite direction from the neural and peripheral tissue effects described above GTEx Portal
Evidence quality The CDH5 pQTL association is reported from a single meta-analysis of two isolated Greek cohorts totaling 2,893 individuals, with external validation in the ORCADES cohort (up to 950 individuals). The study-wide significance threshold was P < 7.45 x 10^-11, and 58.8% of all identified pQTLs replicated in the independent cohort. Because the discovery cohorts are isolated populations, allele frequencies and linkage disequilibrium patterns may differ from broader ancestry groups, which limits generalizability. Effect size and p-value specifically for the rs1049970-CDH5 association were not detailed in the available study text, representing a gap in the evidence summarized here. GTEx eQTL evidence for LINC00920 is based on 953 donors across multiple tissues, with p-values ranging from 2.3e-38 to 2.5e-86 across reported tissues, indicating highly robust statistical support GTEx Portal.
Tissue-specific expression effects
- LINC00920: the alternate allele is associated with increased expression in multiple brain regions (cervical spinal cord, hippocampus, putamen basal ganglia), testis, tibial nerve, and skin (both sun-exposed and non-sun-exposed), while the same allele is associated with reduced expression in whole blood, indicating tissue-dependent regulatory effects GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs1049970?
rs1049970 is a genetic variant identified as a protein quantitative trait locus (pQTL) for CDH5 in a study of 248 cardiometabolic serum proteins. It was also found to influence expression of the nearby gene LINC00920 in a tissue-specific way.
What is a protein QTL and why does it matter?
A protein quantitative trait locus (pQTL) is a genetic variant statistically associated with measured differences in the level of a specific protein in blood or serum. Identifying pQTLs helps researchers understand how genetic variation may influence protein production and relate to disease processes.
Does rs1049970 affect gene expression in the brain?
Yes. GTEx data from 953 donors show the alternate allele of rs1049970 increases LINC00920 expression in the cervical spinal cord, hippocampus, and putamen basal ganglia, as well as in tibial nerve and skin. In contrast, it decreases LINC00920 expression in whole blood.
Was the CDH5 pQTL finding replicated in other populations?
The broader study reported that 58.8% of all identified protein QTLs replicated in an independent cohort from the Orkney Islands in Scotland. Whether rs1049970 specifically was among those replicated variants is not specified in the available study text.
What populations were included in the study?
The pQTL discovery used two isolated Greek cohorts: MANOLIS (n=1,356) and Pomak (n=1,537), totaling 2,893 individuals. Replication was tested in the ORCADES cohort from the Orkney Islands (up to 950 individuals). Results from isolated populations may not generalize equally to all ancestries.