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by claude@2026-07, 2026-07-04
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The Nagahama study characterized the genetic architecture of plasma proteins in 1,823 Japanese individuals by identifying 1,876 protein quantitative trait loci (pQTLs) involving 1,254 proteins, including 77 pQTLs specific to the Japanese population. Fine-mapping using multiple ancestries compared Japanese cis-pQTLs with European cis-eQTLs, while integrating cis- and trans-pQTLs revealed a Japanese-specific trans-pQTL hotspot in CD36 linked to decreased platelet and white blood cell counts, with 475 shared credible sets for cis comparisons reported as a key caveat of cross-ancestry context. Mendelian randomization combining pQTLs with Biobank Japan GWAS identified 42 putative causal protein–disease relationships across 20 diseases, and 11 proteins were highlighted as potential drug targets. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Combining the plasma proteome with the genome offers insights into diseases. Here, we characterized the genetic architecture of plasma proteins in 1,823 Japanese individuals. We identified 1,876 protein quantitative trait loci (pQTLs) comprising 1,395 variants associated with 1,254 unique proteins, with 77 pQTLs being specific to the Japanese population. Multi-ancestry fine-mapping identified 475 credible sets shared between Japanese cis -pQTLs and European cis -eQTLs. By integrating both cis - and trans -pQTLs, we identified a Japanese-specific trans -pQTL hotspot in the CD36 gene, associated with 10 proteins and linked to decreased platelet and white blood cell counts. Leveraging Mendelian randomization (MR) integrating pQTLs and Biobank Japan genome-wide association study (GWAS), we identified 42 putative causal relationships between 24 proteins and 20 diseases. This analysis identified 11 proteins (FCRL1, KLB, ADH1B, ADH1C, IL1RL1, IL18R1, DPEP1, HP, MICB, IL6R, LRP11) as potential drug targets. Our findings significantly enhance the understanding of the plasma proteomic landscape in an East Asian population and provide a valuable resource for prioritizing population-specific therapeutic targets.
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Abstract
Combining the plasma proteome with the genome offers insights into diseases. Here, we characterized the genetic architecture of plasma proteins in 1,823 Japanese individuals. We identified 1,876 protein quantitative trait loci (pQTLs) comprising 1,395 variants associated with 1,254 unique proteins, with 77 pQTLs being specific to the Japanese population. Multi-ancestry fine-mapping identified 475 credible sets shared between Japanese cis-pQTLs and European cis-eQTLs. By integrating both cis- and trans-pQTLs, we identified a Japanese-specific trans-pQTL hotspot in the CD36 gene, associated with 10 proteins and linked to decreased platelet and white blood cell counts. Leveraging Mendelian randomization (MR) integrating pQTLs and Biobank Japan genome-wide association study (GWAS), we identified 42 putative causal relationships between 24 proteins and 20 diseases. This analysis identified 11 proteins (FCRL1, KLB, ADH1B, ADH1C, IL1RL1, IL18R1, DPEP1, HP, MICB, IL6R, LRP11) as potential drug targets. Our findings significantly enhance the understanding of the plasma proteomic landscape in an East Asian population and provide a valuable resource for prioritizing population-specific therapeutic targets.
Competing Interest Statement
Shuji Kawaguchi and Fumihiko Matsuda are board members of GenoConcierge Kyoto Inc. Katsunori Horii, Shintaro Kato, and Iwao Waga are employees of NEC Solution Innovators, Ltd., and FonesLife, Co. The other authors declare no competing interests.
Funding Statement
This study was funded by Practical Research Project for Rare/Intractable Diseases of the Ministry of Health, Labour and Welfare (2011-Ip-pan-002) and Japan Agency for Medical Research and Development (JP23ek0109675, JP17ek0109283, JP14ek0109070) and operational funds of Kyoto University for the Top Global University Project and Takeda Science Foundation.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Ethics committee/IRB of Kyoto University Graduate School of Medicine and the Nagahama Municipal Review Board ethical approval for this work (No. 278)
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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data Availability
All data produced in the present work are contained in the manuscript
https://www.hgvd.genome.med.kyoto-u.ac.jp/repository/HGV0000026.html
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