{"id":"https://openalex.org/W7225664607","doi":"https://doi.org/10.21203/rs.3.rs-11669564/v1","title":"The global population genetics of GPNMB-associated amyloidosis cutis dyschromica: ancestry-specific variation and likely underdiagnosis","display_name":"The global population genetics of GPNMB-associated amyloidosis cutis dyschromica: ancestry-specific variation and likely underdiagnosis","publication_year":2026,"publication_date":"2026-11-10","ids":{"openalex":"https://openalex.org/W7225664607","doi":"https://doi.org/10.21203/rs.3.rs-11669564/v1"},"language":"en","primary_location":{"id":"doi:10.21203/rs.3.rs-11669564/v1","doi":"https://doi.org/10.21203/rs.3.rs-11669564/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11669564/v1","pdf_url":"https://www.researchsquare.com/article/rs-11669564/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-11669564/latest.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5027745665","display_name":"Alan Garc\u00eda\u2010Elfring","orcid":"https://orcid.org/0000-0002-2093-4041","observed_orcids":["https://orcid.org/0000-0002-2093-4041"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Alan Garcia-Elfring","raw_affiliation_strings":["PyType Laboratorio"],"raw_orcid":"https://orcid.org/0000-0002-2093-4041","affiliations":[{"raw_affiliation_string":"PyType Laboratorio","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5027745665"],"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/T11642","display_name":"Genomics and Rare Diseases","score":0.7705000042915344,"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/T11642","display_name":"Genomics and Rare Diseases","score":0.7705000042915344,"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/T11305","display_name":"Amyloidosis: Diagnosis, Treatment, Outcomes","score":0.07639999687671661,"subfield":{"id":"https://openalex.org/subfields/2724","display_name":"Internal 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/T11144","display_name":"melanin and skin pigmentation","score":0.07289999723434448,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell Biology"},"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/gpnmb","display_name":"GPNMB","score":0.9980000257492065},{"id":"https://openalex.org/keywords/loss-of-function-variants","display_name":"loss-of-function mutations","score":0.8659999966621399},{"id":"https://openalex.org/keywords/carrier-frequency","display_name":"carrier frequency","score":0.6970000267028809},{"id":"https://openalex.org/keywords/underdiagnosis","display_name":"underdiagnosis","score":0.7059999704360962},{"id":"https://openalex.org/keywords/recessive-inheritance","display_name":"recessive inheritance","score":0.8140000104904175},{"id":"https://openalex.org/keywords/pigmentary-disorders","display_name":"skin pigmentation disorders","score":0.8230000138282776},{"id":"https://openalex.org/keywords/ashkenazi-jews","display_name":"Ashkenazi Jews","score":0.8529999852180481},{"id":"https://openalex.org/keywords/latin-america","display_name":"Latin America","score":0.7409999966621399},{"id":"https://openalex.org/keywords/gnomad","display_name":"gnomAD","score":0.4650000035762787}],"concepts":[{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.6816999912261963},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.6208999752998352},{"id":"https://openalex.org/C195054827","wikidata":"https://www.wikidata.org/wiki/Q504568","display_name":"Founder effect","level":5,"score":0.5296000242233276},{"id":"https://openalex.org/C16671776","wikidata":"https://www.wikidata.org/wiki/Q5420592","display_name":"Exome sequencing","level":4,"score":0.445499986410141},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.44020000100135803},{"id":"https://openalex.org/C37463918","wikidata":"https://www.wikidata.org/wiki/Q387981","display_name":"Allele frequency","level":4,"score":0.427700012922287},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.41269999742507935},{"id":"https://openalex.org/C12125453","wikidata":"https://www.wikidata.org/wiki/Q5156837","display_name":"Compound heterozygosity","level":4,"score":0.40639999508857727},{"id":"https://openalex.org/C10590036","wikidata":"https://www.wikidata.org/wiki/Q417664","display_name":"Exome","level":5,"score":0.40059998631477356},{"id":"https://openalex.org/C137916694","wikidata":"https://www.wikidata.org/wiki/Q1549382","display_name":"Asymptomatic carrier","level":3,"score":0.37389999628067017},{"id":"https://openalex.org/C175783326","wikidata":"https://www.wikidata.org/wiki/Q185055","display_name":"Mendelian inheritance","level":3,"score":0.36629998683929443},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.36329999566078186},{"id":"https://openalex.org/C75069973","wikidata":"https://www.wikidata.org/wiki/Q913584","display_name":"Genetic genealogy","level":3,"score":0.36070001125335693},{"id":"https://openalex.org/C68873052","wikidata":"https://www.wikidata.org/wiki/Q349856","display_name":"Genetic variation","level":3,"score":0.3409000039100647},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.32499998807907104},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.30790001153945923},{"id":"https://openalex.org/C2778745941","wikidata":"https://www.wikidata.org/wiki/Q2735907","display_name":"Cutis laxa","level":2,"score":0.2888999879360199},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.287200003862381},{"id":"https://openalex.org/C2779951007","wikidata":"https://www.wikidata.org/wiki/Q816798","display_name":"Amyloidosis","level":2,"score":0.2833999991416931},{"id":"https://openalex.org/C31467283","wikidata":"https://www.wikidata.org/wiki/Q912147","display_name":"Genotyping","level":4,"score":0.26910001039505005},{"id":"https://openalex.org/C40583040","wikidata":"https://www.wikidata.org/wiki/Q1502105","display_name":"Human genetic variation","level":5,"score":0.26499998569488525},{"id":"https://openalex.org/C64474127","wikidata":"https://www.wikidata.org/wiki/Q1071953","display_name":"Medical genetics","level":3,"score":0.26170000433921814},{"id":"https://openalex.org/C85721925","wikidata":"https://www.wikidata.org/wiki/Q31151","display_name":"Population genetics","level":3,"score":0.25699999928474426},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.2556000053882599},{"id":"https://openalex.org/C2780673598","wikidata":"https://www.wikidata.org/wiki/Q285223","display_name":"Genetic testing","level":2,"score":0.25029999017715454}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.21203/rs.3.rs-11669564/v1","doi":"https://doi.org/10.21203/rs.3.rs-11669564/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11669564/v1","pdf_url":"https://www.researchsquare.com/article/rs-11669564/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-11669564/v1","doi":"https://doi.org/10.21203/rs.3.rs-11669564/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11669564/v1","pdf_url":"https://www.researchsquare.com/article/rs-11669564/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":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320331257","display_name":"Alliance de recherche num\u00e9rique du Canada","ror":"https://ror.org/010r6td27"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225664607.pdf","grobid_xml":"https://content.openalex.org/works/W7225664607.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W7220834255"],"related_works":["https://openalex.org/W2783286524","https://openalex.org/W4322614950","https://openalex.org/W3190759662","https://openalex.org/W3127081087","https://openalex.org/W3133583939","https://openalex.org/W2949716162","https://openalex.org/W2954436320","https://openalex.org/W7148979771","https://openalex.org/W4413106883","https://openalex.org/W3207867298"],"abstract_inverted_index":{"Abstract":[0],"Amyloidosis":[1],"cutis":[2],"dyschromica":[3],"(ACD)":[4],"is":[5,31,147,218,227,238],"a":[6,150,228],"rare":[7],"recessive":[8,197],"pigmentary":[9,256],"disorder":[10],"caused":[11],"by":[12,85,149],"biallelic":[13,62,119],"loss-of-function":[14],"(LoF)":[15],"variants":[16,50],"in":[17,71,75,81,89,95,103,184,241],"GPNMB":[18,209,250],".":[19],"Almost":[20],"all":[21],"reported":[22,127,141],"patients":[23,142],"are":[24,115,168],"East":[25,78,259],"or":[26,38,133],"Southeast":[27],"Asian,":[28],"and":[29,56,60,77,91,108,172,222,226,244,248],"it":[30],"unknown":[32],"whether":[33],"this":[34],"reflects":[35],"allele":[36],"distribution":[37],"ascertainment.":[39],"Using":[40],"gnomAD":[41,159],"v4.1,":[42],"I":[43],"identified":[44],"114":[45],"high-confidence":[46],"predicted":[47],"LoF":[48],"(pLoF)":[49],"on":[51,252],"the":[52,202,208],"MANE":[53],"Select":[54],"transcript":[55],"estimated":[57],"carrier":[58],"frequencies":[59,68],"expected":[61,116],"prevalence":[63],"across":[64,192],"ancestry":[65],"groups.":[66],"Carrier":[67],"were":[69,213],"highest":[70],"Ashkenazi":[72,111,134,145,246],"Jewish":[73,135],"(1":[74,80,88,94],"251)":[76],"Asian":[79],"261)":[82],"individuals,":[83],"followed":[84],"non-Finnish":[86],"Europeans":[87,171],"358)":[90],"Admixed":[92,162,223],"Americans":[93],"422).":[96],"Under":[97],"Hardy\u2013Weinberg":[98],"proportions,":[99],"about":[100,109],"183":[101],"people":[102],"Mexico":[104],"(95%":[105],"interval":[106],"141\u2013344)":[107],"40":[110],"Jews":[112],"worldwide":[113],"(25\u201368)":[114],"to":[117,220],"carry":[118],"pLoF":[120,166,182],"alleles.":[121],"A":[122],"literature":[123],"audit":[124],"found":[125],"no":[126,190],"ACD":[128,237],"cases":[129],"of":[130,157,165,207],"Latin":[131,242],"American":[132,224],"origin,":[136],"against":[137],"at":[138],"least":[139],"100":[140],"worldwide.":[143],"The":[144],"burden":[146],"driven":[148],"single":[151],"founder":[152],"splice-donor":[153],"allele,":[154],"c.367+2T>C":[155],"(57":[156],"80":[158],"copies).":[160],"In":[161],"Americans,":[163],"70%":[164],"alleles":[167,177],"shared":[169],"with":[170,196],"30%":[173],"come":[174],"from":[175],"four":[176],"essentially":[178],"absent":[179],"elsewhere.":[180],"Heterozygous":[181],"carriers":[183],"394,841":[185],"UK":[186],"Biobank":[187],"exomes":[188],"showed":[189],"association":[191],"4,529":[193],"traits,":[194],"consistent":[195],"inheritance.":[198],"Variants":[199],"that":[200,236,249],"disrupt":[201],"essential":[203],"MITF":[204],"binding":[205],"site":[206],"proximal":[210],"promoter":[211],"(MCS3)":[212],"rare,":[214],"but":[215],"one,":[216],"7-23246653-A-T,":[217],"confined":[219],"African":[221],"chromosomes":[225],"candidate":[229],"for":[230,255],"functional":[231],"testing.":[232],"These":[233],"results":[234],"indicate":[235],"likely":[239],"underdiagnosed":[240],"America":[243],"among":[245],"Jews,":[247],"belongs":[251],"diagnostic":[253],"panels":[254],"disorders":[257],"beyond":[258],"Asia.":[260]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}