{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:21Z","timestamp":1791385041337,"version":"4.3.3"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>SOD1<\/jats:italic>\n                      gene encodes superoxide dismutase 1, an antioxidant enzyme in which pathogenic variants cause a subset of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although the clinical and molecular consequences of\n                      <jats:italic>SOD1<\/jats:italic>\n                      variants are well established, its locus\u2010wide population genetic architecture has not been systematically characterized across global populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To characterize patterns of genetic diversity, population differentiation, and evolutionary constraint across the\n                      <jats:italic>SOD1<\/jats:italic>\n                      locus in worldwide human populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed genomic variation spanning the\n                      <jats:italic>SOD1<\/jats:italic>\n                      region in the five continental populations of the 1000 Genomes Project. Nucleotide diversity (\u03c0), fixation index (FST), and allele frequency distributions were estimated using sliding\u2010window analyses. Bootstrap resampling was used to compare diversity within and outside the coding region. Recent positive selection was assessed using XP\u2010nSL, and codon\u2010based evolutionary analyses were performed using primate\n                      <jats:italic>SOD1<\/jats:italic>\n                      orthologs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The coding region consistently exhibited a twofold to threefold reduction in nucleotide diversity relative to adjacent genomic sequences across all populations. Bootstrap analyses confirmed significantly lower diversity within the locus than in flanking regions (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 in all populations). Population differentiation was low (mean FST \u2248 0.03) and showed no pronounced peaks within the coding interval, whereas allele frequency distributions were broadly similar across continental populations. XP\u2010nSL analyses detected no evidence of population\u2010specific recent selective sweeps. Codon\u2010based analyses identified only 31 variable codons among 155 analyzed positions, six codons under negative selection, and no evidence of positive selection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>SOD1<\/jats:italic>\n                      locus exhibits reduced standing genetic variation, limited continental differentiation, and strong evolutionary conservation, consistent with sustained functional constraint. These findings provide a comprehensive population genetic framework for interpreting genetic variation at this medically important locus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70052","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:29:00Z","timestamp":1786969740000},"page":"340-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population\u2010Level Nucleotide Diversity and Genetic Differentiation at\n                    <i>SOD1<\/i>\n                    Across Global Human Populations"],"prefix":"10.1111","volume":"90","author":[{"given":"Sergio V.","family":"Flores","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Medicina de Altura, Vicerrector\u00eda de Investigaci\u00f3n e Innovaci\u00f3n Universidad Arturo Prat  Iquique Chile"},{"name":"Laboratorio de Gen\u00e9tica Neuropsiqui\u00e1trica (LabGen) Departamento de Psiquiatr\u00eda y Salud Mental Sur Facultad de Medicina Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Lillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica Neuropsiqui\u00e1trica (LabGen) Departamento de Psiquiatr\u00eda y Salud Mental Sur Facultad de Medicina Universidad de Chile  Santiago Chile"},{"name":"Departamento de Neurolog\u00eda y Neurocirug\u00eda Sur, Facultad de Medicina Universidad de Chile  Santiago Chile"},{"name":"Unidad de Neurolog\u00eda Hospital San Jos\u00e9  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Brice\u00f1o\u2010Moya","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica Neuropsiqui\u00e1trica (LabGen) Departamento de Psiquiatr\u00eda y Salud Mental Sur Facultad de Medicina Universidad de Chile  Santiago Chile"},{"name":"Facultad de Ciencias de la Salud Universidad Cat\u00f3lica Ra\u00fal Silva Henr\u00edquez  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000586"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2010.03.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00479\u20104"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201003891\u20108"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000516752"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102018\u2010319386"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu605"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msi105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1582668"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010325921"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12101544"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.01.016"}],"container-title":["Annals 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