{"doi":"10.17615/32b0-5485","title":"Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study","abstract":"Arsenic toxicokinetics are important for disease risks in exposed populations, but genetic determinants are not fully understood. We examined urine arsenic species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study participants 18 years of age and older with data on ∼400 genome-wide microsatellite markers spaced ∼10 cM and arsenic speciation (683 participants from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit-transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also conducted principal component analyses of the logit % arsenic species. We used inverse-normalized residuals from multivariable-adjusted polygenic heritability analysis for multipoint variance components linkage analysis. We also examined the contribution of polymorphisms in the arsenic metabolism gene AS3MT via conditional linkage analysis. We localized a quantitative trait locus (QTL) on chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal component of logit % arsenic species). This peak was partially but not fully explained by measured AS3MT variants. We also localized a QTL for the second principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that was not evident from considering % arsenic species individually. Some other loci were suggestive or significant for 1 geographical area but not overall across all areas, indicating possible locus heterogeneity. This genome-wide linkage scan suggests genetic determinants of arsenic toxicokinetics to be identified by future fine-mapping, and illustrates the utility of principal component analysis as a novel approach that considers % arsenic species jointly.","journal":"UNC Libraries","year":2020,"id":140219,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9171,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75356,"name":"Frank D. Gilliland","orcid":"0000-0002-9033-7269","position":1,"is_corresponding":false},{"id":604512,"name":"Walter Goessler","orcid":"0000-0002-0142-9373","position":2,"is_corresponding":false},{"id":597648,"name":"Sandra Laston","orcid":null,"position":3,"is_corresponding":false},{"id":604513,"name":"Poojitha Balakrishnan","orcid":"0000-0002-8513-5865","position":4,"is_corresponding":false},{"id":604514,"name":"Matthew O. Gribble","orcid":"0000-0002-1614-2981","position":5,"is_corresponding":false},{"id":25148,"name":"Duncan C. Thomas","orcid":"0000-0002-6040-8804","position":6,"is_corresponding":false},{"id":340280,"name":"Kevin A. Francesconi","orcid":"0000-0002-2536-0542","position":7,"is_corresponding":false},{"id":532081,"name":"Karin Haack","orcid":"0000-0003-3067-3575","position":8,"is_corresponding":false},{"id":11361,"name":"Kari E. North","orcid":"0000-0002-8903-0366","position":9,"is_corresponding":false},{"id":288772,"name":"Ana Navas‐Acién","orcid":"0000-0001-9824-7797","position":10,"is_corresponding":false},{"id":24742,"name":"Nora Franceschini","orcid":"0009-0001-8346-3662","position":11,"is_corresponding":false},{"id":385449,"name":"V. Saroja Voruganti","orcid":"0000-0002-8704-4529","position":12,"is_corresponding":false},{"id":246476,"name":"Shelley A. Cole","orcid":"0000-0002-2651-0127","position":13,"is_corresponding":false},{"id":390060,"name":"Jason G. Umans","orcid":"0000-0002-2746-3350","position":14,"is_corresponding":false},{"id":604511,"name":"María Téllez-Plaza","orcid":"0000-0002-3850-1228","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:17.077903Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}