{"id":"https://openalex.org/W2765604752","doi":"https://doi.org/10.48550/arxiv.1710.10641","title":"A Fast, Accurate Two-Step Linear Mixed Model for Genetic Analysis Applied to Repeat MRI Measurements","display_name":"A Fast, Accurate Two-Step Linear Mixed Model for Genetic Analysis Applied to Repeat MRI Measurements","publication_year":2017,"publication_date":"2017-10-29","ids":{"openalex":"https://openalex.org/W2765604752","doi":"https://doi.org/10.48550/arxiv.1710.10641","mag":"2765604752"},"language":"en","primary_location":{"id":"pmh:oai:arXiv.org:1710.10641","doi":null,"is_oa":true,"landing_page_url":"http://arxiv.org/abs/1710.10641","pdf_url":"https://arxiv.org/pdf/1710.10641","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},"volume":null,"type":"preprint","indexed_in":["arxiv","datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://arxiv.org/pdf/1710.10641","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5106697667","display_name":"Qifan Yang","orcid":"https://orcid.org/0000-0002-4151-5882","observed_orcids":["https://orcid.org/0000-0002-4151-5882"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yang, Qifan","raw_affiliation_strings":[". Computational Biology and Bioinformatics , Department of Biological Sciences , University of Southern California , California , 90089 , USA;",". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Computational Biology and Bioinformatics , Department of Biological Sciences , University of Southern California , California , 90089 , USA;","institution_ids":["https://openalex.org/I1174212"]},{"raw_affiliation_string":". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029373833","display_name":"Gennady V. Roshchupkin","orcid":"https://orcid.org/0000-0002-3403-2313","observed_orcids":["https://orcid.org/0000-0002-3403-2313"]},"institutions":[{"id":"https://openalex.org/I2801952686","display_name":"Erasmus MC","ror":"https://ror.org/018906e22","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2801952686"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Roshchupkin, Gennady V.","raw_affiliation_strings":[". Department of Medical Informatics, Radiology & Nuclear Medicine , Erasmus MC , Rotterdam , The Netherlands ;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Department of Medical Informatics, Radiology & Nuclear Medicine , Erasmus MC , Rotterdam , The Netherlands ;","institution_ids":["https://openalex.org/I2801952686"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038384386","display_name":"Wiro J. Niessen","orcid":"https://orcid.org/0000-0002-5822-1995","observed_orcids":["https://orcid.org/0000-0002-5822-1995"]},"institutions":[{"id":"https://openalex.org/I2801952686","display_name":"Erasmus MC","ror":"https://ror.org/018906e22","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2801952686"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Niessen, Wiro J.","raw_affiliation_strings":[". Department of Medical Informatics, Radiology & Nuclear Medicine , Erasmus MC , Rotterdam , The Netherlands ;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Department of Medical Informatics, Radiology & Nuclear Medicine , Erasmus MC , Rotterdam , The Netherlands ;","institution_ids":["https://openalex.org/I2801952686"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011519020","display_name":"Sarah Elizabeth Medland","orcid":"https://orcid.org/0000-0003-1382-380X","observed_orcids":["https://orcid.org/0000-0003-1382-380X"]},"institutions":[{"id":"https://openalex.org/I217937681","display_name":"QIMR Berghofer Medical Research Institute","ror":"https://ror.org/004y8wk30","country_code":"AU","type":"facility","lineage":["https://openalex.org/I217937681"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Medland, Sarah E.","raw_affiliation_strings":[". Queensland , Institute of Medical Research , Berghofer Medical Research Institute , Royal Brisbane Hospital , Brisbane , QLD 4029 Australia;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Queensland , Institute of Medical Research , Berghofer Medical Research Institute , Royal Brisbane Hospital , Brisbane , QLD 4029 Australia;","institution_ids":["https://openalex.org/I217937681"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066345371","display_name":"Alyssa H. Zhu","orcid":"https://orcid.org/0000-0003-0083-5107","observed_orcids":["https://orcid.org/0000-0003-0083-5107"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Zhu, Alyssa H.","raw_affiliation_strings":[". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100606557","display_name":"Paul M. Thompson","orcid":"https://orcid.org/0000-0002-4720-8867","observed_orcids":["https://orcid.org/0000-0002-4720-8867","https://orcid.org/0000-0003-2476-2803","https://orcid.org/0000-0002-2305-8438"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Thompson, Paul M.","raw_affiliation_strings":[". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019781190","display_name":"Neda Jahanshad","orcid":"https://orcid.org/0000-0003-4401-8950","observed_orcids":["https://orcid.org/0000-0003-4401-8950"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jahanshad, Neda","raw_affiliation_strings":[". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;","University  of Southern California"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":". Imaging Genetics Center , Stevens Neuroimaging and Informatics Institute , Keck School of Medicine , University of Southern California , Marina del Rey , California , 90292 , USA;","institution_ids":["https://openalex.org/I1174212"]},{"raw_affiliation_string":"University  of Southern California","institution_ids":["https://openalex.org/I1174212"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"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":0.9208999872207642,"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":0.9208999872207642,"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":0.05889999866485596,"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/T11468","display_name":"Genetic Mapping and Diversity in Plants and Animals","score":0.00430000014603138,"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/linear-mixed-models","display_name":"linear mixed models","score":0.7409999966621399},{"id":"https://openalex.org/keywords/heritability-estimation","display_name":"heritability estimation","score":0.8370000123977661},{"id":"https://openalex.org/keywords/hippocampal-volume","display_name":"hippocampal volume","score":0.7720000147819519},{"id":"https://openalex.org/keywords/genetic-association","display_name":"genetic association","score":0.578000009059906},{"id":"https://openalex.org/keywords/computational-complexity","display_name":"computational complexity","score":0.6060000061988831},{"id":"https://openalex.org/keywords/relatedness","display_name":"relatedness","score":0.5929999947547913},{"id":"https://openalex.org/keywords/population-structure","display_name":"population structure","score":0.9279999732971191},{"id":"https://openalex.org/keywords/uk-biobank","display_name":"UK Biobank","score":0.7480000257492065},{"id":"https://openalex.org/keywords/non-iterative-algorithm","display_name":"non-iterative algorithm","score":0.6129999756813049}],"concepts":[{"id":"https://openalex.org/C116567970","wikidata":"https://www.wikidata.org/wiki/Q864217","display_name":"Biobank","level":2,"score":0.7358834147453308},{"id":"https://openalex.org/C161890455","wikidata":"https://www.wikidata.org/wiki/Q1503548","display_name":"Heritability","level":2,"score":0.6659496426582336},{"id":"https://openalex.org/C153720581","wikidata":"https://www.wikidata.org/wiki/Q5532490","display_name":"Generalized linear mixed model","level":2,"score":0.6213127374649048},{"id":"https://openalex.org/C119043178","wikidata":"https://www.wikidata.org/wiki/Q320723","display_name":"Covariate","level":2,"score":0.5917333960533142},{"id":"https://openalex.org/C163175372","wikidata":"https://www.wikidata.org/wiki/Q3339222","display_name":"Linear model","level":2,"score":0.5499019026756287},{"id":"https://openalex.org/C16012445","wikidata":"https://www.wikidata.org/wiki/Q1501135","display_name":"Mixed model","level":2,"score":0.5366112589836121},{"id":"https://openalex.org/C129848803","wikidata":"https://www.wikidata.org/wiki/Q2564360","display_name":"Sample size determination","level":2,"score":0.5313540101051331},{"id":"https://openalex.org/C106934330","wikidata":"https://www.wikidata.org/wiki/Q1971873","display_name":"Trait","level":2,"score":0.5212229490280151},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.49819469451904297},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.47510015964508057},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.4608544707298279},{"id":"https://openalex.org/C196083921","wikidata":"https://www.wikidata.org/wiki/Q7915758","display_name":"Variance (accounting)","level":2,"score":0.4289158582687378},{"id":"https://openalex.org/C198531522","wikidata":"https://www.wikidata.org/wiki/Q485146","display_name":"Sample (material)","level":2,"score":0.4122909605503082},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.39950549602508545},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.30364328622817993},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.18930232524871826},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.1645614206790924},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.13685515522956848},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.12769019603729248},{"id":"https://openalex.org/C144133560","wikidata":"https://www.wikidata.org/wiki/Q4830453","display_name":"Business","level":0,"score":0.0},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.0},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.0},{"id":"https://openalex.org/C121955636","wikidata":"https://www.wikidata.org/wiki/Q4116214","display_name":"Accounting","level":1,"score":0.0},{"id":"https://openalex.org/C43617362","wikidata":"https://www.wikidata.org/wiki/Q170050","display_name":"Chromatography","level":1,"score":0.0},{"id":"https://openalex.org/C99454951","wikidata":"https://www.wikidata.org/wiki/Q932068","display_name":"Environmental health","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:arXiv.org:1710.10641","doi":null,"is_oa":true,"landing_page_url":"http://arxiv.org/abs/1710.10641","pdf_url":"https://arxiv.org/pdf/1710.10641","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},{"id":"doi:10.48550/arxiv.1710.10641","doi":"https://doi.org/10.48550/arxiv.1710.10641","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.1710.10641","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Preprint"}],"best_oa_location":{"id":"pmh:oai:arXiv.org:1710.10641","doi":null,"is_oa":true,"landing_page_url":"http://arxiv.org/abs/1710.10641","pdf_url":"https://arxiv.org/pdf/1710.10641","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},"sustainable_development_goals":[],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":21,"referenced_works":["https://openalex.org/W1966775465","https://openalex.org/W1971298736","https://openalex.org/W1980168725","https://openalex.org/W1990209919","https://openalex.org/W2011085530","https://openalex.org/W2025071037","https://openalex.org/W2033151532","https://openalex.org/W2045217506","https://openalex.org/W2079927753","https://openalex.org/W2096916467","https://openalex.org/W2113253256","https://openalex.org/W2118347577","https://openalex.org/W2119586206","https://openalex.org/W2150248909","https://openalex.org/W2153860431","https://openalex.org/W2156123885","https://openalex.org/W2272246971","https://openalex.org/W2522628945","https://openalex.org/W2574432813","https://openalex.org/W2612069075","https://openalex.org/W2747404963"],"related_works":["https://openalex.org/W2908742687","https://openalex.org/W4402348572","https://openalex.org/W4225504409","https://openalex.org/W2949174501","https://openalex.org/W3162006506","https://openalex.org/W4224222412","https://openalex.org/W1993284865","https://openalex.org/W4402225327","https://openalex.org/W4396966057","https://openalex.org/W2014686650"],"abstract_inverted_index":{"Large-scale":[0],"biobanks":[1],"are":[2,80,177],"being":[3],"collected":[4,43],"around":[5],"the":[6,90,93,97,112,149,156,161,187,203,220],"world":[7],"in":[8,192],"efforts":[9],"to":[10,53,102,185,199],"better":[11],"understand":[12],"human":[13],"health":[14],"and":[15,34,59,69,82,126,211,222,230,233],"risk":[16],"factors":[17],"for":[18,105],"disease.":[19],"They":[20],"often":[21],"survey":[22],"hundreds":[23],"of":[24,26,38,48,62,85,92,99,114,155,160,190],"thousands":[25],"individuals,":[27],"combining":[28],"questionnaires":[29],"with":[30,143,239],"clinical,":[31],"genetic,":[32],"demographic,":[33],"imaging":[35],"assessments;":[36],"some":[37],"this":[39],"data":[40,201,214],"may":[41],"be":[42],"longitudinally.":[44],"Genetic":[45],"associations":[46],"analysis":[47],"such":[49],"datasets":[50],"requires":[51],"methods":[52],"properly":[54],"handle":[55],"relatedness,":[56],"population":[57],"structure":[58],"other":[60],"types":[61],"biases":[63],"introduced":[64],"by":[65,89,165],"confounders.":[66],"Most":[67],"popular":[68],"accurate":[70,127,153,235],"approaches":[71],"rely":[72],"on":[73],"linear":[74],"mixed":[75],"model":[76],"(LMM)":[77],"algorithms,":[78],"which":[79,206],"iterative":[81],"computational":[83,138],"complexity":[84,139],"each":[86],"iteration":[87],"scales":[88,141],"square":[91],"sample":[94,144],"size,":[95],"slowing":[96],"pace":[98],"discoveries":[100],"(up":[101],"several":[103],"days":[104],"single":[106],"trait":[107,162],"analysis),":[108],"and,":[109],"furthermore,":[110],"limiting":[111],"use":[113],"repeat":[115],"phenotypic":[116],"measurements.":[117],"Here,":[118],"we":[119],"describe":[120],"our":[121],"new,":[122],"non-iterative,":[123],"much":[124],"faster":[125,183],"Two-Step":[128,197],"Linear":[129],"Mixed":[130],"Model":[131],"(Two-Step":[132],"LMM)":[133],"approach,":[134],"that":[135,140,148],"has":[136],"a":[137,182],"linearly":[142],"size.":[145],"We":[146,195,218],"show":[147],"first":[150],"step":[151,180],"retains":[152],"estimates":[154],"heritability":[157,236],"(the":[158],"proportion":[159],"variance":[163],"explained":[164],"additive":[166],"genetic":[167,173],"factors),":[168],"even":[169],"when":[170],"increasingly":[171],"complex":[172],"relationships":[174],"between":[175],"individuals":[176],"modeled.":[178],"Second":[179],"provides":[181],"framework":[184],"obtain":[186],"effect":[188],"sizes":[189],"covariates":[191],"regression":[193],"model.":[194],"applied":[196],"LMM":[198],"real":[200],"from":[202,215],"UK":[204],"Biobank,":[205],"recently":[207],"released":[208],"genotyping":[209],"information":[210],"processed":[212],"MRI":[213],"9,725":[216],"individuals.":[217],"used":[219],"left":[221],"right":[223],"hippocampus":[224],"volume":[225],"(HV)":[226],"as":[227],"repeated":[228],"measures,":[229],"observed":[231],"increased":[232],"more":[234],"estimation,":[237],"consistent":[238],"simulations.":[240]},"counts_by_year":[],"updated_date":"2026-10-13T10:08:12.033832","created_date":"2017-11-10T00:00:00"}
