{"id":"https://openalex.org/W7225646144","doi":"https://doi.org/10.21203/rs.3.rs-11323482/v1","title":"Genetic Heterogeneity of Familial Dyslipidemia: Real-World Evidence from a Large Colombian Cohort","display_name":"Genetic Heterogeneity of Familial Dyslipidemia: Real-World Evidence from a Large Colombian Cohort","publication_year":2026,"publication_date":"2026-11-09","ids":{"openalex":"https://openalex.org/W7225646144","doi":"https://doi.org/10.21203/rs.3.rs-11323482/v1"},"language":"en","primary_location":{"id":"doi:10.21203/rs.3.rs-11323482/v1","doi":"https://doi.org/10.21203/rs.3.rs-11323482/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11323482/v1","pdf_url":"https://www.researchsquare.com/article/rs-11323482/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.researchsquare.com/article/rs-11323482/latest.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5108986048","display_name":"Laura Camila Rios Pinto","orcid":"https://orcid.org/0009-0008-9901-4395","observed_orcids":["https://orcid.org/0009-0008-9901-4395"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Laura Camila Rios Pinto","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015462830","display_name":"Jessica Andrea Ovalle Torres","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jessica Andrea Ovalle Torres","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006288371","display_name":"Carlos Estrada\u2010Serrato","orcid":"https://orcid.org/0000-0001-9071-6990","observed_orcids":["https://orcid.org/0000-0001-9071-6990"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Carlos Estrada-Serrato","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093006309","display_name":"Paula Rueda\u2010Gait\u00e1n","orcid":"https://orcid.org/0000-0003-2209-9913","observed_orcids":["https://orcid.org/0000-0003-2209-9913"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paula Rueda-Gaitan","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161333704","display_name":"Diego Alejandro Pinto-Pinz\u00f3n","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210164215","display_name":"Fundaci\u00f3n Universitaria Sanitas","ror":"https://ror.org/05pfpea66","country_code":"CO","type":"education","lineage":["https://openalex.org/I4210164215"]}],"countries":["CO"],"is_corresponding":false,"raw_author_name":"Diego Alejandro Pinto-Pinz\u00f3n","raw_affiliation_strings":["Fundaci\u00f3n Universitaria Sanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fundaci\u00f3n Universitaria Sanitas","institution_ids":["https://openalex.org/I4210164215"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161360063","display_name":"Taryn A Castro-Cuesta","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Taryn A Castro-Cuesta","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055843775","display_name":"Mario A. Isaza-Ruget","orcid":"https://orcid.org/0000-0003-0243-9263","observed_orcids":["https://orcid.org/0000-0003-0243-9263"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mario Isaza-Ruget","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5074012041","display_name":"Juan Javier L\u00f3pez Rivera","orcid":"https://orcid.org/0000-0003-4989-4853","observed_orcids":["https://orcid.org/0000-0003-4989-4853"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Juan Javier L\u00f3pez Rivera","raw_affiliation_strings":["Cl\u00ednica Colsanitas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cl\u00ednica Colsanitas","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"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/T10394","display_name":"Lipoproteins and Cardiovascular Health","score":0.9086999893188477,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10394","display_name":"Lipoproteins and Cardiovascular Health","score":0.9086999893188477,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.05849999934434891,"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/T13430","display_name":"Lipid metabolism and disorders","score":0.02239999920129776,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/familial-dyslipidemia","display_name":"familial dyslipidemia","score":0.9980000257492065},{"id":"https://openalex.org/keywords/familial-hypercholesterolemia","display_name":"familial hypercholesterolemia","score":0.9629999995231628},{"id":"https://openalex.org/keywords/ldlr-variants","display_name":"LDLR variants","score":0.7599999904632568},{"id":"https://openalex.org/keywords/apolipoprotein-b","display_name":"apolipoprotein B","score":0.7039999961853027},{"id":"https://openalex.org/keywords/lipoprotein-lipase","display_name":"lipoprotein lipase","score":0.9789999723434448},{"id":"https://openalex.org/keywords/copy-number-variation","display_name":"copy number variation","score":0.7319999933242798},{"id":"https://openalex.org/keywords/genetic-counseling","display_name":"genetic counseling","score":0.4490000009536743},{"id":"https://openalex.org/keywords/colombian-population","display_name":"Colombian population","score":0.5379999876022339},{"id":"https://openalex.org/keywords/premature-cardiovascular-disease","display_name":"premature cardiovascular disease","score":0.578000009059906},{"id":"https://openalex.org/keywords/whole-exome-sequencing","display_name":"exome sequencing","score":0.6880000233650208},{"id":"https://openalex.org/keywords/variant-interpretation","display_name":"variant interpretation","score":0.33000001311302185},{"id":"https://openalex.org/keywords/familial-hypertriglyceridemia","display_name":"familial hypertriglyceridemia","score":0.5730000138282776}],"concepts":[{"id":"https://openalex.org/C2779120738","wikidata":"https://www.wikidata.org/wiki/Q2711291","display_name":"Familial hypercholesterolemia","level":3,"score":0.6786999702453613},{"id":"https://openalex.org/C64618202","wikidata":"https://www.wikidata.org/wiki/Q3733697","display_name":"Genetic heterogeneity","level":4,"score":0.6366000175476074},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6075999736785889},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.5863999724388123},{"id":"https://openalex.org/C2780948078","wikidata":"https://www.wikidata.org/wiki/Q21130010","display_name":"PCSK9","level":5,"score":0.5472999811172485},{"id":"https://openalex.org/C64474127","wikidata":"https://www.wikidata.org/wiki/Q1071953","display_name":"Medical genetics","level":3,"score":0.5217999815940857},{"id":"https://openalex.org/C62746215","wikidata":"https://www.wikidata.org/wiki/Q14890615","display_name":"Apolipoprotein B","level":3,"score":0.5145000219345093},{"id":"https://openalex.org/C2778096610","wikidata":"https://www.wikidata.org/wiki/Q1476525","display_name":"Dyslipidemia","level":3,"score":0.48739999532699585},{"id":"https://openalex.org/C167135981","wikidata":"https://www.wikidata.org/wiki/Q2146302","display_name":"Retrospective cohort study","level":2,"score":0.3986999988555908},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3873000144958496},{"id":"https://openalex.org/C16671776","wikidata":"https://www.wikidata.org/wiki/Q5420592","display_name":"Exome sequencing","level":4,"score":0.3702999949455261},{"id":"https://openalex.org/C149923435","wikidata":"https://www.wikidata.org/wiki/Q37732","display_name":"Demography","level":1,"score":0.3653999865055084},{"id":"https://openalex.org/C201903717","wikidata":"https://www.wikidata.org/wiki/Q1778788","display_name":"Cohort study","level":2,"score":0.3594000041484833},{"id":"https://openalex.org/C200544954","wikidata":"https://www.wikidata.org/wiki/Q516389","display_name":"Penetrance","level":4,"score":0.3587999939918518},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.3529999852180481},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.35190001130104065},{"id":"https://openalex.org/C187212893","wikidata":"https://www.wikidata.org/wiki/Q123028","display_name":"Pediatrics","level":1,"score":0.33980000019073486},{"id":"https://openalex.org/C80227256","wikidata":"https://www.wikidata.org/wiki/Q1124169","display_name":"Genetic counseling","level":2,"score":0.3183000087738037},{"id":"https://openalex.org/C10590036","wikidata":"https://www.wikidata.org/wiki/Q417664","display_name":"Exome","level":5,"score":0.31529998779296875},{"id":"https://openalex.org/C2781179581","wikidata":"https://www.wikidata.org/wiki/Q2857712","display_name":"Family history","level":2,"score":0.29490000009536743},{"id":"https://openalex.org/C107130276","wikidata":"https://www.wikidata.org/wiki/Q133805","display_name":"Epidemiology","level":2,"score":0.2745000123977661},{"id":"https://openalex.org/C43554185","wikidata":"https://www.wikidata.org/wiki/Q425649","display_name":"LDL receptor","level":4,"score":0.274399995803833},{"id":"https://openalex.org/C195054827","wikidata":"https://www.wikidata.org/wiki/Q504568","display_name":"Founder effect","level":5,"score":0.2727999985218048},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.26820001006126404},{"id":"https://openalex.org/C2780673598","wikidata":"https://www.wikidata.org/wiki/Q285223","display_name":"Genetic testing","level":2,"score":0.26170000433921814},{"id":"https://openalex.org/C164866538","wikidata":"https://www.wikidata.org/wiki/Q367351","display_name":"Cluster (spacecraft)","level":2,"score":0.2612999975681305},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2587999999523163}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.21203/rs.3.rs-11323482/v1","doi":"https://doi.org/10.21203/rs.3.rs-11323482/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11323482/v1","pdf_url":"https://www.researchsquare.com/article/rs-11323482/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.21203/rs.3.rs-11323482/v1","doi":"https://doi.org/10.21203/rs.3.rs-11323482/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11323482/v1","pdf_url":"https://www.researchsquare.com/article/rs-11323482/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"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":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225646144.pdf","grobid_xml":"https://content.openalex.org/works/W7225646144.grobid-xml"},"referenced_works_count":30,"referenced_works":["https://openalex.org/W1569405015","https://openalex.org/W2010412420","https://openalex.org/W2040120597","https://openalex.org/W2051978340","https://openalex.org/W2057394745","https://openalex.org/W2127199991","https://openalex.org/W2166446665","https://openalex.org/W2169874695","https://openalex.org/W2476752993","https://openalex.org/W2555950699","https://openalex.org/W2592589825","https://openalex.org/W2786782798","https://openalex.org/W2892369001","https://openalex.org/W2941884731","https://openalex.org/W3015517289","https://openalex.org/W3021549637","https://openalex.org/W3106630897","https://openalex.org/W3164259959","https://openalex.org/W4205876099","https://openalex.org/W4223478923","https://openalex.org/W4244733450","https://openalex.org/W4280507817","https://openalex.org/W4310493849","https://openalex.org/W4379016641","https://openalex.org/W4396512442","https://openalex.org/W4399434761","https://openalex.org/W4403331093","https://openalex.org/W4409252811","https://openalex.org/W4417441916","https://openalex.org/W7126021714"],"related_works":["https://openalex.org/W4410849862","https://openalex.org/W2892459295","https://openalex.org/W7214628493","https://openalex.org/W2885600577","https://openalex.org/W2535260643","https://openalex.org/W4416841885","https://openalex.org/W2943851754","https://openalex.org/W2056139841","https://openalex.org/W7116953774","https://openalex.org/W4417427855"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Familial":[2],"dyslipidemia":[3],"(FD)":[4],"comprises":[5],"a":[6,75,84,107,181,267,291,332,347],"heterogeneous":[7],"group":[8],"of":[9,12,35,78,129,173,258,280,301,307,316,329,356],"genetic":[10,33,48,303,318,344,372],"disorders":[11],"lipoprotein":[13],"metabolism":[14],"associated":[15],"with":[16,20,74,163,229,283],"premature":[17],"cardiovascular":[18],"disease,":[19],"familial":[21],"hypercholesterolemia":[22,164],"being":[23],"the":[24,32,51,89,126,171,174,196,204,217,254,259,298,302,308,317,324,353,357,363,379,395],"most":[25,325],"extensively":[26],"characterized.":[27],"Despite":[28],"their":[29],"clinical":[30,76,151],"relevance,":[31],"architecture":[34],"FD":[36,330,392],"remains":[37],"poorly":[38],"described":[39],"in":[40,50,156,161,193,210,221,240,247,275,331],"Latin":[41],"American":[42,127],"populations,":[43],"limiting":[44],"risk":[45],"stratification":[46],"and":[47,56,117,132,150,153,160,186,213,225,242,278],"counseling":[49],"region.":[52],"Methods":[53],"A":[54,239],"retrospective":[55],"pragmatic":[57],"cohort":[58,334],"study":[59,322],"(September":[60],"2020\u2013July":[61],"2025)":[62],"was":[63,141,154,202],"conducted":[64],"on":[65],"860":[66],"Colombian":[67,256,333,358,396],"patients":[68,96,162],"referred":[69],"for":[70,170,365,382,391],"whole-exome":[71],"sequencing":[72],"(WES)":[73],"suspicion":[77],"FD.":[79],"Patients":[80],"were":[81,122,208,219],"recruited":[82],"from":[83],"national":[85,383],"reference":[86],"laboratory":[87],"serving":[88],"EPS":[90],"Sanitas":[91],"healthcare":[92],"network.":[93],"While":[94],"all":[95],"underwent":[97],"WES,":[98],"analysis":[99],"strategies":[100],"included":[101,253],"616":[102],"targeted":[103],"exomes":[104],"(filtered":[105],"through":[106],"gene":[108,168],"panel);":[109],"additionally,":[110],"198":[111],"singleton":[112],"exomes,":[113,116],"42":[114],"trio":[115],"4":[118],"duo":[119],"exomes.":[120],"Variants":[121],"classified":[123],"according":[124,147],"to":[125,148,180,335,337,387],"College":[128],"Medical":[130],"Genetics":[131],"Genomics":[133],"(ACMG)":[134],"criteria.":[135],"Results":[136],"The":[137,166,199,340],"overall":[138],"positivity":[139,206,299],"rate":[140,145,300],"14.88%":[142],"(128/860).":[143],"This":[144,321],"varied":[146],"age":[149],"phenotype":[152],"highest":[155,205],"young":[157],"adults":[158],"(21.83%)":[159],"(17.39%).":[165],"LDLR":[167,194,236,263,269],"accounted":[169],"majority":[172],"positive":[175],"findings":[176,252,315,341],"(94":[177],"variants),":[178],"followed":[179],"lesser":[182],"extent":[183],"by":[184,233],"APOB":[185],"LPL":[187],";":[188],"fourteen":[189],"large":[190],"deletions":[191],"(CNVs)":[192],"completed":[195],"molecular":[197],"landscape.":[198],"geographic":[200],"distribution":[201],"heterogeneous:":[203],"rates":[207],"recorded":[209,220],"Magdalena":[211],"(42.86%)":[212],"Sucre":[214],"(37.50%),":[215],"while":[216],"lowest":[218],"Bogot\u00e1":[222],"(~":[223],"11%)":[224],"Antioquia":[226],"(<":[227],"10%),":[228],"specific":[230],"variants":[231],"clustering":[232],"region":[234],"(e.g.,":[235],"c.11G":[237],">":[238,245,265,272],"Cesar":[241],"Bogot\u00e1;":[243],"c.1246C":[244],"T":[246],"Tolima\u2013Caldas\u2013Valle":[248],"del":[249],"Cauca).":[250],"Notable":[251],"first":[255],"case":[257],"Lebanese":[260],"allele":[261],"(":[262],"c.2043C":[264],"A),":[266],"novel":[268],"variant":[270],"(c.1955T":[271],"G)":[273],"segregating":[274],"two":[276],"sisters,":[277],"0.58%":[279],"cases":[281],"presenting":[282],"homozygous":[284],"dyslipidemia.":[285],"Additionally,":[286],"our":[287,338],"results":[288,361],"demonstrated":[289],"that":[290],"larger":[292],"panel":[293],"size":[294],"does":[295],"not":[296],"increase":[297],"test;":[304],"specifically,":[305],"25":[306],"37":[309],"genes":[310],"(67.6%)":[311],"yielded":[312],"no":[313],"diagnostic":[314],"test.":[319],"Conclusions":[320],"represents":[323],"extensive":[326],"genomic":[327],"characterization":[328],"date":[336],"knowledge.":[339],"reveal":[342],"marked":[343],"heterogeneity":[345],"without":[346],"single":[348],"dominant":[349],"founder":[350],"allele,":[351],"reflecting":[352],"ancestral":[354],"admixture":[355],"population.":[359],"These":[360],"support":[362],"need":[364,381],"more":[366],"selective,":[367],"clinically":[368],"impact-driven":[369],"criteria":[370],"when":[371],"testing":[373],"is":[374],"requested.":[375],"Furthermore,":[376],"they":[377],"underscore":[378],"urgent":[380],"cascade":[384],"screening":[385],"programs":[386],"make":[388],"precision":[389],"medicine":[390],"accessible":[393],"throughout":[394],"territory.":[397]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}