rs113003549 (CDH4): Plasma Protein Level Variant

Key takeaways

• rs113003549 is associated with CDH4 (Cadherin-4) protein levels measured in blood plasma
• The association was found using mass spectrometry, which can detect true protein changes that antibody-based tests might miss or misreport
• The discovery cohort included 1,260 individuals, with replication attempted in 325 additional participants
• This is a preliminary finding from a smaller-scale study compared to the largest proteomics GWAS datasets available

What the research says A genome-wide association study (GWAS) using mass spectrometry (MS)-based proteomics analyzed 1,980 proteins quantified from blood plasma samples, identifying 364 protein quantitative trait loci (pQTLs) in a discovery cohort of 1,260 individuals from the USA, with 102 replicated in a cohort of 325 individuals from Asia and 35 reported as previously undescribed. The study used the Seer Proteograph nanoparticle enrichment platform, which, unlike antibody-based affinity proteomics tools, can help distinguish whether a genetic variant truly changes protein abundance or whether it merely alters the region of the protein that an antibody or aptamer physically binds to (an "epitope effect"), a distinction that matters because epitope effects can produce misleading signals in affinity-based studies. Across previously reported pQTLs evaluated in this dataset, approximately 30% were confirmed as consistent with true protein abundance changes and another 30% could not be replicated, with epitope effects identified as one possible explanation for non-replication.

Reported associations

• CDH4 protein levels in blood plasma: rs113003549 was identified as a pQTL - a genetic variant linked to measured protein levels - for CDH4 (Cadherin-4) in blood plasma, detected using a mass spectrometry nanoparticle enrichment proteomics platform in a discovery cohort of 1,260 individuals

Evidence quality The study relied on a discovery cohort of 1,260 individuals from the USA and a replication cohort of 325 individuals from Asia - substantially smaller than the largest existing affinity-based proteomics GWAS studies, which range from roughly 35,000 to over 54,000 participants. The study reports 364 pQTLs identified in discovery and 102 replicated, but the available study text does not specify whether rs113003549 was among those replicated or among the 35 newly reported variants. The evidence for this specific variant should therefore be treated as preliminary pending confirmation in larger, independent cohorts. The MS-based methodology does offer an advantage over affinity platforms in distinguishing genuine protein abundance changes from epitope artifacts, which strengthens the biological plausibility of identified signals.

Lifestyle considerations No lifestyle considerations on file for this variant.