{"id":"https://openalex.org/W4401667443","doi":"https://doi.org/10.1101/2024.08.15.608197","title":"Analysis of 3.6 million individuals yields minimal evidence of pairwise genetic interactions for height","display_name":"Analysis of 3.6 million individuals yields minimal evidence of pairwise genetic interactions for height","publication_year":2024,"publication_date":"2024-08-17","ids":{"openalex":"https://openalex.org/W4401667443","doi":"https://doi.org/10.1101/2024.08.15.608197"},"language":"en","primary_location":{"id":"doi:10.1101/2024.08.15.608197","doi":"https://doi.org/10.1101/2024.08.15.608197","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1101/2024.08.15.608197","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://dx.doi.org/10.1101/2024.08.15.608197","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5061878724","display_name":"Mohammad Reza Jabalameli","orcid":"https://orcid.org/0000-0002-7762-0529","observed_orcids":["https://orcid.org/0000-0002-7762-0529"]},"institutions":[{"id":"https://openalex.org/I4210097491","display_name":"23andMe (United States)","ror":"https://ror.org/00q62jx03","country_code":"US","type":"company","lineage":["https://openalex.org/I4210097491"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"M.Reza Jabalameli","raw_affiliation_strings":["23andMe, Inc., Sunnyvale, California, USA"],"raw_orcid":"https://orcid.org/0000-0002-7762-0529","affiliations":[{"raw_affiliation_string":"23andMe, Inc., Sunnyvale, California, USA","institution_ids":["https://openalex.org/I4210097491"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055374455","display_name":"Michael Vaclav Holmes","orcid":"https://orcid.org/0000-0001-6617-0879","observed_orcids":["https://orcid.org/0000-0001-6617-0879"]},"institutions":[{"id":"https://openalex.org/I4210097491","display_name":"23andMe (United States)","ror":"https://ror.org/00q62jx03","country_code":"US","type":"company","lineage":["https://openalex.org/I4210097491"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael V Holmes","raw_affiliation_strings":["23andMe, Inc., Sunnyvale, California, USA"],"raw_orcid":"https://orcid.org/0000-0001-6617-0879","affiliations":[{"raw_affiliation_string":"23andMe, Inc., Sunnyvale, California, USA","institution_ids":["https://openalex.org/I4210097491"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056201449","display_name":"David A. Hinds","orcid":"https://orcid.org/0000-0002-4911-803X","observed_orcids":["https://orcid.org/0000-0002-4911-803X"]},"institutions":[{"id":"https://openalex.org/I4210097491","display_name":"23andMe (United States)","ror":"https://ror.org/00q62jx03","country_code":"US","type":"company","lineage":["https://openalex.org/I4210097491"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Hinds","raw_affiliation_strings":["23andMe, Inc., Sunnyvale, California, USA"],"raw_orcid":"https://orcid.org/0000-0002-4911-803X","affiliations":[{"raw_affiliation_string":"23andMe, Inc., Sunnyvale, California, USA","institution_ids":["https://openalex.org/I4210097491"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047245152","display_name":"Adam Auton","orcid":"https://orcid.org/0000-0002-1630-1225","observed_orcids":["https://orcid.org/0000-0002-1630-1225"]},"institutions":[{"id":"https://openalex.org/I4210097491","display_name":"23andMe (United States)","ror":"https://ror.org/00q62jx03","country_code":"US","type":"company","lineage":["https://openalex.org/I4210097491"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Adam Auton","raw_affiliation_strings":["23andMe, Inc., Sunnyvale, California, USA"],"raw_orcid":"https://orcid.org/0000-0002-1630-1225","affiliations":[{"raw_affiliation_string":"23andMe, Inc., Sunnyvale, California, USA","institution_ids":["https://openalex.org/I4210097491"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5066806444","display_name":"Pierre Fontanillas","orcid":"https://orcid.org/0000-0002-8944-4454","observed_orcids":["https://orcid.org/0000-0002-8944-4454"]},"institutions":[{"id":"https://openalex.org/I4210097491","display_name":"23andMe (United States)","ror":"https://ror.org/00q62jx03","country_code":"US","type":"company","lineage":["https://openalex.org/I4210097491"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Pierre Fontanillas","raw_affiliation_strings":["23andMe, Inc., Sunnyvale, California, USA"],"raw_orcid":"https://orcid.org/0000-0002-8944-4454","affiliations":[{"raw_affiliation_string":"23andMe, Inc., Sunnyvale, California, USA","institution_ids":["https://openalex.org/I4210097491"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5047245152","https://openalex.org/A5066806444"],"corresponding_institution_ids":["https://openalex.org/I4210097491"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13354","display_name":"Genetics and Physical Performance","score":0.006399999838322401,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10594","display_name":"Genetic and phenotypic traits in livestock","score":0.0032999999821186066,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/adult-height","display_name":"adult height","score":0.9850000143051147},{"id":"https://openalex.org/keywords/epistasis","display_name":"epistasis","score":0.828000009059906},{"id":"https://openalex.org/keywords/gene-gene-interaction","display_name":"gene-gene interaction","score":0.718999981880188},{"id":"https://openalex.org/keywords/nonadditive-genetic-effects","display_name":"non-additive genetic effects","score":0.8930000066757202},{"id":"https://openalex.org/keywords/polygenic-architecture","display_name":"polygenic architecture","score":0.7829999923706055},{"id":"https://openalex.org/keywords/narrow-sense-heritability","display_name":"narrow-sense heritability","score":0.8100000023841858},{"id":"https://openalex.org/keywords/broad-sense-heritability","display_name":"broad-sense heritability","score":0.902999997138977},{"id":"https://openalex.org/keywords/genome-wide-association-study","display_name":"genome-wide association study","score":0.6169999837875366},{"id":"https://openalex.org/keywords/european-ancestry","display_name":"European ancestry","score":0.7269999980926514},{"id":"https://openalex.org/keywords/dominance-effects","display_name":"dominance effects","score":0.4099999964237213}],"concepts":[{"id":"https://openalex.org/C61727976","wikidata":"https://www.wikidata.org/wiki/Q751748","display_name":"Epistasis","level":3,"score":0.7921098470687866},{"id":"https://openalex.org/C161890455","wikidata":"https://www.wikidata.org/wiki/Q1503548","display_name":"Heritability","level":2,"score":0.7194852828979492},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5936692953109741},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.56858891248703},{"id":"https://openalex.org/C139275648","wikidata":"https://www.wikidata.org/wiki/Q17134011","display_name":"SNP","level":5,"score":0.5474486947059631},{"id":"https://openalex.org/C106934330","wikidata":"https://www.wikidata.org/wiki/Q1971873","display_name":"Trait","level":2,"score":0.521821916103363},{"id":"https://openalex.org/C127808970","wikidata":"https://www.wikidata.org/wiki/Q385989","display_name":"Bonferroni correction","level":2,"score":0.5157954692840576},{"id":"https://openalex.org/C104201883","wikidata":"https://www.wikidata.org/wiki/Q4681342","display_name":"Additive genetic effects","level":3,"score":0.5124185681343079},{"id":"https://openalex.org/C184898388","wikidata":"https://www.wikidata.org/wiki/Q1435712","display_name":"Pairwise comparison","level":2,"score":0.46852725744247437},{"id":"https://openalex.org/C203223496","wikidata":"https://www.wikidata.org/wiki/Q4681344","display_name":"Additive model","level":2,"score":0.4636704921722412},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.4519387185573578},{"id":"https://openalex.org/C151913843","wikidata":"https://www.wikidata.org/wiki/Q3454555","display_name":"Dominance (genetics)","level":3,"score":0.43799933791160583},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.43508750200271606},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.4333533048629761},{"id":"https://openalex.org/C153209595","wikidata":"https://www.wikidata.org/wiki/Q501128","display_name":"Single-nucleotide polymorphism","level":4,"score":0.4145391285419464},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.32518982887268066},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.17504793405532837},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.13306421041488647},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.08237171173095703},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2024.08.15.608197","doi":"https://doi.org/10.1101/2024.08.15.608197","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1101/2024.08.15.608197","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2024.08.15.608197","doi":"https://doi.org/10.1101/2024.08.15.608197","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1101/2024.08.15.608197","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.46810001134872437,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Observational Study","id":"https://openalex.org/study-designs/observational-study"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":37,"referenced_works":["https://openalex.org/W1975931018","https://openalex.org/W1977636169","https://openalex.org/W1988694228","https://openalex.org/W2021793145","https://openalex.org/W2053824472","https://openalex.org/W2067328319","https://openalex.org/W2072214908","https://openalex.org/W2076011171","https://openalex.org/W2076611182","https://openalex.org/W2090713084","https://openalex.org/W2094189284","https://openalex.org/W2104382557","https://openalex.org/W2110808585","https://openalex.org/W2139852278","https://openalex.org/W2155496693","https://openalex.org/W2156995578","https://openalex.org/W2157308673","https://openalex.org/W2161998322","https://openalex.org/W2166787058","https://openalex.org/W2188707104","https://openalex.org/W2240954615","https://openalex.org/W2742857851","https://openalex.org/W2793543636","https://openalex.org/W2950944031","https://openalex.org/W2971517243","https://openalex.org/W2982183508","https://openalex.org/W3083180505","https://openalex.org/W3137716414","https://openalex.org/W3146958471","https://openalex.org/W3147973671","https://openalex.org/W3187545772","https://openalex.org/W4229079875","https://openalex.org/W4304698823","https://openalex.org/W4376868470","https://openalex.org/W4386789188","https://openalex.org/W4387301321","https://openalex.org/W4392559581"],"related_works":["https://openalex.org/W2170858721","https://openalex.org/W2155496693","https://openalex.org/W3133690674","https://openalex.org/W2171540772","https://openalex.org/W1879996786","https://openalex.org/W7096702673","https://openalex.org/W2754233740","https://openalex.org/W1988694228","https://openalex.org/W7098194262","https://openalex.org/W4304808851"],"abstract_inverted_index":{"Abstract":[0],"Adult":[1],"height":[2,29,104],"is":[3],"a":[4,91,121,147,178,183],"highly":[5],"heritable":[6],"polygenic":[7],"trait":[8],"with":[9,26,66,103,131,172,221],"heritability":[10,56],"attributable":[11],"to":[12,22,28,63,71,96],"thousands":[13],"of":[14,33,74,80,113,134,166,187,194,213,218,233,237,243],"independent":[15,99],"variants.":[16],"Large-scale":[17],"studies":[18,60],"have":[19,61],"been":[20],"able":[21],"detect":[23],"genetic":[24,43,82,241],"variants":[25,65],"contributions":[27],"in":[30,46,84,239],"the":[31,50,72,85,164,211,234,240],"range":[32],"approximately":[34],"1.2":[35],"millimetre":[36],"per":[37],"allele":[38],"copy":[39],"on":[40],"average.":[41],"Non-additive":[42],"interactions":[44,168,196,215],"may,":[45],"part,":[47],"account":[48],"for":[49,111,141,163,204],"difference":[51],"between":[52,216],"broad-sense":[53],"and":[54,108,154,158,173],"narrow-sense":[55],"estimates.":[57],"However,":[58],"prior":[59],"failed":[62],"identify":[64],"non-additive":[67,114],"effects,":[68],"possibly":[69],"due":[70],"lack":[73],"statistical":[75],"power.":[76],"Leveraging":[77],"3.6M":[78],"individuals":[79],"European":[81],"ancestry":[83],"23andMe":[86],"research":[87],"cohort,":[88],"we":[89,145,190],"performed":[90],"genome-wide":[92],"analysis":[93,208,229],"study":[94],"(GWAS)":[95],"select":[97],"1,063":[98],"common":[100],"SNPs":[101],"associated":[102],"(p-value":[105,137],"<":[106,138,202],"5e-8),":[107],"then":[109],"screened":[110],"evidence":[112,133,193,232],"effects":[115],"by":[116,169],"analysing":[117],"564,453":[118],"models":[119,130,171],"including":[120,151],"pairwise":[122,129],"SNP-SNP":[123,135],"interaction":[124,136],"term.":[125],"We":[126,161],"identified":[127],"69":[128],"suggestive":[132],"1e-4)":[139],"and,":[140],"each":[142],"SNP":[143],"pair,":[144],"evaluated":[146],"fully":[148],"saturated":[149],"model":[150],"additive,":[152],"dominant,":[153],"epistatic":[155,167,175,195,214],"(additive-by-additive,":[156],"additive-by-dominance":[157],"dominance-by-dominance)":[159],"terms.":[160],"tested":[162],"presence":[165],"comparing":[170],"without":[174],"terms":[176],"using":[177],"likelihood":[179],"ratio":[180,198],"test.":[181],"Assuming":[182],"strict":[184],"Bonferroni-corrected":[185],"threshold":[186],"8.9e-8":[188],"(0.05/564,453),":[189],"found":[191],"no":[192],"(Likelihood":[197],"test":[199],"(LRT)":[200],"p-value":[201],"9e-07":[203],"all":[205],"models).":[206],"Our":[207,227],"rules":[209],"out":[210],"existence":[212],"alleles":[217],">1%":[219],"frequency":[220],"effect":[222],"sizes":[223],"larger":[224],"than":[225],"2.42mm.":[226],"large-scale":[228],"provides":[230],"further":[231],"minimal":[235],"contribution":[236],"non-additivity":[238],"architecture":[242],"adult":[244],"human":[245],"height.":[246]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1}],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2024-08-18T00:00:00"}
