[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-426252-105":59,"doc-detail-426252-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","long-life-family-study-participants-carry-rare-variants-that-correlate-with-better-cognitive-function","LONG LIFE FAMILY STUDY - Participants Carry Rare Variants That Correlate With Better Cognitive Function","","Cognitive impairment poses an increasing healthcare and quality-of-life threat as populations age. Using genome-wide association studies in the Long Life Family Study (LLFS), the research tests genetic factors tied to nine neuropsychological outcomes, then contrasts findings with UK Biobank for cognitive ability and reaction time. Quantitative trait locus analyses integrate whole-blood transcriptomic and serum metabolomic data, and gene set enrichment evaluates nominal signals. Twelve genome-wide significant variants across seven LLFS tests show domain-specific replication, with rare protective and deleterious variants mapping to distinct functional pathways.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/long-life-family-study-participants-carry-rare-variants-that-correlate-with-better-cognitive-function/426252/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/long-life-family-study-participants-carry-rare-variants-that-correlate-with-better-cognitive-function/426252.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-16","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address?","Question",{"text":112,"@type":113},"The study seeks genetic factors underlying cognitive function, especially how rare variants relate to better or worse cognitive performance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were genetic signals identified and validated?",{"text":117,"@type":113},"The authors performed GWAS across nine neuropsychological test scores in the Long Life Family Study and compared results with UK Biobank GWAS, including replication patterns by test.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the QTL analyses and pathway enrichment reveal?",{"text":121,"@type":113},"QTL analyses found limited significant SNP–transcript links and no significant SNP–lipid or SNP–polar metabolite associations, while gene set enrichment identified three pathways including KEGG JAK-STAT signaling and oxidative phosphorylation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},426252,1790892601,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":8,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":81},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","1134 Innovation in Aging, 2025, Vol. 9, No. S2  \nAbstract citation ID: igaf122.3805  \nLONG LIFE FAMILY STUDY PARTICIPANTS CARRY RARE VARIANTS THAT CORRELATE WITH BETTER COGNITIVE FUNCTION  \nHannah Lords1, Mengze Li1, Zeyuan Song2,  \nAnastasia Leshchyk2, Harold Bae3, Stacy Andersen1, Anastasia Gurinovich2, and Paola Sebastiani2, 1. Boston University, Boston, Massachusetts, United States, 2. Tufts Medical Center, Boston, Massachusetts, United States,  \n3. Oregon State University, Corvallis, Oregon, United States Cognitive impairment is a growing healthcare and  \nquality-of-life challenge as more individuals reach older ages. Without effective interventions, the prevalence of decline will continue to rise. To identify genetic factors underlying cognitive function, we performed GWAS on nine neuropsychological test scores in the Long Life Family Study (LLFS). We then compared results with UK Biobank GWAS of general cognitive ability and reaction time, conducted quantitative trait locus (QTL) analyses of whole blood transcriptomic and serum metabolomic data for genome-wide significant variants (p \u003C 5e-8), and performed gene set enrichment analyses of nominally significant transcripts. We identified 12 genome-wide significant variants across 7 tests in LLFS. Comparison with UK Biobank data revealed test-specific replication patterns, suggesting that loci for general cognitive function and reaction time reflect distinct cognitive domains. QTL analyses identified one SNP–transcript association (p \u003C 0.05/16,300) but no significant SNP–lipid or SNP–polar metabolite associations. Three rare protective variants—rs190287985, rs75730801, and rs552842447—were linked to semantic fluency (animal), phonemic fluency (FAS), and digit span forward, respectively. Two rare deleterious variants, rs556333682 and rs188304645, associated with performance on the Hopkins Verbal Learning Test (HVLT) total recall, lie in ischemia-related genes SH3TC1 and RPH3A. Another variant, rs180691759, associated with HVLT delayed recall, was proximal to RSPO3 and linked to decreased ECHDC1 expression, implicating ischemic and unexplained ethylmalonic acid pathways. Gene set enrichment identified three pathways (FDR \u003C 0.05), including KEGG JAK-STAT signaling and oxidative phosphorylation. These findings highlight domain-specific mechanisms of cognitive resilience and decline.","cbCaicnatl94P9ms","https://ap.wps.com/l/cbCaicnatl94P9ms","pdf",999946,"English","# Abstract\n## Study purpose and design\n## Genetic association and replication\n## QTL and gene set enrichment findings\n## Implications for cognitive resilience","[{\"question\":\"What question does the study address?\",\"answer\":\"The study seeks genetic factors underlying cognitive function, especially how rare variants relate to better or worse cognitive performance.\"},{\"question\":\"How were genetic signals identified and validated?\",\"answer\":\"The authors performed GWAS across nine neuropsychological test scores in the Long Life Family Study and compared results with UK Biobank GWAS, including replication patterns by test.\"},{\"question\":\"What did the QTL analyses and pathway enrichment reveal?\",\"answer\":\"QTL analyses found limited significant SNP–transcript links and no significant SNP–lipid or SNP–polar metabolite associations, while gene set enrichment identified three pathways including KEGG JAK-STAT signaling and oxidative phosphorylation.\"}]","LONG LIFE FAMILY STUDY - Participants Carry Rare Variants That Correlate With Better Cognitive Function | PDF",1790639955]