{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:45:56Z","timestamp":1791776756556,"version":"4.3.4"},"reference-count":105,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32670077"],"award-info":[{"award-number":["32670077"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200548"],"award-info":[{"award-number":["32200548"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Research on genetic variants affecting the gut microbiome and blood metabolites has mainly focused on single nucleotide variants (SNPs), leaving structural variants (SVs) largely unexplored. Here, we analyzed high\u2010coverage (\u223c42\u00d7) whole\u2010genome sequencing data from 2002 individuals and constructed a catalog of 138\u00a0859 high\u2010confidence SVs, including 44.3% variants not represented in public SV resources. Genome\u2010wide association analyses of 22\u00a0519 common SVs identified 30 microbiome\u2010associated and 48 metabolite\u2010associated SV loci, including 19 study\u2010wide significant associations. Notable signals included an Asian\u2010specific 6.5k deletion at\n                    <jats:italic>TENT2<\/jats:italic>\n                    associated with\n                    <jats:italic>Coprobacillus sp. 29_1<\/jats:italic>\n                    abundance (\u03b2 = 0.158,\n                    <jats:italic>p<\/jats:italic>\n                    = 2.5 \u00d7 10\n                    <jats:sup>\u22129<\/jats:sup>\n                    ) and a deletion covering\n                    <jats:italic>HBA1\/HBA2\/HBM\/HBQ1<\/jats:italic>\n                    linked to nine blood metabolic traits (strongest for MCV; \u03b2 = \u20100.570,\n                    <jats:italic>p<\/jats:italic>\n                    = 1.22 \u00d7 10\n                    <jats:sup>\u221291<\/jats:sup>\n                    ). Conditional and variance\u2010partitioning analyses indicated that SVs capture complementary genetic information beyond tested SNP signals. SV\u2010based Mendelian randomization delineated putative directional relationships, including\n                    <jats:italic>Clostridium ramosum<\/jats:italic>\n                    with serum uric acid and hyperuricemia. In vitro experiments further supported three predicted metabolite\u2013microbe interactions, showing that vitamin K1 inhibited\n                    <jats:italic>Coprococcus comes<\/jats:italic>\n                    , hydroxyproline inhibited\n                    <jats:italic>Veillonella parvula<\/jats:italic>\n                    , and cysteine promoted\n                    <jats:italic>Fusobacterium mortiferum<\/jats:italic>\n                    growth. Together, our study provides a comprehensive SVs resource and highlights SVs as overlooked genetic determinants of host\u2010microbiome\u2010metabolome interactions relevant to human physiology and disease.\n                  <\/jats:p>","DOI":"10.1002\/advs.78201","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:10:46Z","timestamp":1791774646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Variants in the Human Genome Associated With Gut Microbiome and Blood Metabolic Traits With Potential Causal Links"],"prefix":"10.1002","author":[{"given":"Qun","family":"Zhou","sequence":"first","affiliation":[{"name":"BGI Research  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genome and Multi\u2010Omics Technologies BGI Research  Shenzhen 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