{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:22:05Z","timestamp":1790612525633,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["825741"],"award-info":[{"award-number":["825741"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P\u2009=\u20091\u2009\u00d7\u200910\u22123) and disorders related to short gestation and low birth weight (P\u2009=\u20093\u2009\u00d7\u200910\u22124). The major indigenous populations in Chile are Aymara\u2013Quechua in the north of the country and the Mapuche\u2013Huilliche in the south. The individual proportion of Aymara\u2013Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P\u2009=\u20094\u2009\u00d7\u200910\u22125), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara\u2013Quechua ancestry proportion (P\u2009=\u20094\u2009\u00d7\u200910\u22124) and 5% per 1% Mapuche\u2013Huilliche ancestry proportion (P\u2009=\u20092\u2009\u00d7\u200910\u22123). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine.<\/jats:p>","DOI":"10.1093\/hmg\/ddab302","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T19:44:26Z","timestamp":1634154266000},"page":"975-984","source":"Crossref","is-referenced-by-count":5,"title":["Inbreeding, Native American ancestry and child mortality: linking human selection and paediatric medicine"],"prefix":"10.1093","volume":"31","author":[{"given":"Fabienne","family":"Koenigstein","sequence":"first","affiliation":[{"name":"Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Boekstegers","sequence":"additional","affiliation":[{"name":"Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Global Health Research, Usher Institute, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland"},{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Fuentes-Guajardo","sequence":"additional","affiliation":[{"name":"Departamento de Tecnolog\u00eda M\u00e9dica, Facultad de Ciencias de la Salud, Tarapac\u00e1 University, Arica, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Gonzalez-Jose","sequence":"additional","affiliation":[{"name":"Instituto Patag\u00f3nico de Ciencias Sociales y Humanas, Centro Nacional Patag\u00f3nico, CONICET, Puerto Madryn, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Bedoya","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda, Grupo Genmol, Universidad de Antioqu\u00eda, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C\u00e1tira","family":"Bortolini","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias, Universidad Federal do Rio Grande do Sul, Puerto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Acu\u00f1a-Alonzo","sequence":"additional","affiliation":[{"name":"National Institute of Anthropology and History, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Gallo","sequence":"additional","affiliation":[{"name":"Laboratorios de Investigaci\u00f3n y Desarrollo, Facultad de Ciencias y Filosof\u00eda, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Ruiz Linares","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China"},{"name":"Aix-Marseille Universit\u00e9, CNRS, EFS, ADES, Marseille, France"},{"name":"Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Rothhammer","sequence":"additional","affiliation":[{"name":"Instituto de Alta Investigaci\u00f3n, Tarapac\u00e1 University, Arica, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justo","family":"Lorenzo Bermejo","sequence":"additional","affiliation":[{"name":"Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"2022032516100827000_ref1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1086\/302661","article-title":"Long homozygous chromosomal segments in reference families from the Centre d'Etude du polymorphisme humain","volume":"65","author":"Broman","year":"1999","journal-title":"Am. 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Commun."},{"key":"2022032516100827000_ref18","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s00125-002-0887-5","article-title":"The association between components of adult height and type II diabetes and insulin resistance: British Women's heart and health study","volume":"45","author":"Lawlor","year":"2002","journal-title":"Diabetologia"},{"key":"2022032516100827000_ref19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/hrt.2003.019950","article-title":"Associations of components of adult height with coronary heart disease in postmenopausal women: the British women\u2019s heart and health study","volume":"90","author":"Lawlor","year":"2004","journal-title":"Heart"},{"key":"2022032516100827000_ref20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/jech.54.2.97","article-title":"Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality","volume":"54","author":"Smith","year":"2000","journal-title":"J. Epidemiol. Community Health"},{"key":"2022032516100827000_ref21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/oxfordjournals.epirev.a000809","article-title":"Height, leg length, and cancer risk: a systematic review","volume":"23","author":"Gunnell","year":"2001","journal-title":"Epidemiol. Rev."},{"key":"2022032516100827000_ref22","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.1038\/s41467-020-19595-y","article-title":"Autozygosity influences cardiometabolic disease-associated traits in the AWI-gen sub-Saharan African study","volume":"11","author":"Ceballos","year":"2020","journal-title":"Nat. Commun."},{"key":"2022032516100827000_ref23","volume-title":"Race mixture in the history of Latin America","author":"M\u00f6rner","year":"1967"},{"key":"2022032516100827000_ref24","doi-asserted-by":"publisher","first-page":"e1004572","DOI":"10.1371\/journal.pgen.1004572","article-title":"Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals","volume":"10","author":"Ruiz-Linares","year":"2014","journal-title":"PLoS Genet."},{"key":"2022032516100827000_ref25","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.gtc.2010.02.011","article-title":"Epidemiology of gallbladder cancer","volume":"39","author":"Eslick","year":"2010","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"2022032516100827000_ref26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1136\/gutjnl-2013-305033","article-title":"The burden of stomach cancer in indigenous populations: a systematic review and global assessment","volume":"63","author":"Arnold","year":"2014","journal-title":"Gut"},{"key":"2022032516100827000_ref27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jaci.2014.07.053","article-title":"Genetic ancestry influences asthma susceptibility and lung function among Latinos","volume":"135","author":"Pino-Yanes","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"2022032516100827000_ref28","doi-asserted-by":"publisher","first-page":"e0141260","DOI":"10.1371\/journal.pone.0141260","article-title":"The relationship between native American ancestry, body mass index and diabetes risk among Mexican-Americans","volume":"10","author":"Hu","year":"2015","journal-title":"PLoS One"},{"key":"2022032516100827000_ref29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ajhg.2014.11.010","article-title":"The genetic ancestry of African Americans, Latinos, and European Americans across the United States","volume":"96","author":"Bryc","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2022032516100827000_ref30","doi-asserted-by":"crossref","first-page":"580","DOI":"10.2105\/AJPH.83.4.580","article-title":"Reported asthma among Puerto Rican, Mexican-American, and Cuban children, 1982 through 1984","volume":"83","author":"Carter-Pokras","year":"1993","journal-title":"Am. J. Public Health"},{"key":"2022032516100827000_ref31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/gepi.20079","article-title":"Genetic admixture and asthma-related phenotypes in Mexican American and Puerto Rican asthmatics","volume":"29","author":"Salari","year":"2005","journal-title":"Genet. Epidemiol."},{"key":"2022032516100827000_ref32","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1590\/S0036-36342007000400012","article-title":"Review of health research on indigenous populations in Latin America, 1995-2004","volume":"49","author":"San Sebastian","year":"2007","journal-title":"Salud Publica Mex."},{"key":"2022032516100827000_ref33","doi-asserted-by":"publisher","first-page":"e1006756","DOI":"10.1371\/journal.pgen.1006756","article-title":"Subtypes of native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile","volume":"13","author":"Lorenzo Bermejo","year":"2017","journal-title":"PLoS Genet."},{"key":"2022032516100827000_ref34","doi-asserted-by":"publisher","first-page":"comment2007.1","DOI":"10.1186\/gb-2001-2-8-comment2007","article-title":"Complex genetic diseases: controversy over the Croesus code","volume":"2","author":"Wright","year":"2001","journal-title":"Genome Biol."},{"key":"2022032516100827000_ref35","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.2028254","article-title":"Reproductive behavior and health in consanguineous marriages","volume":"252","author":"Bittles","year":"1991","journal-title":"Science (New York, N.Y.)"},{"key":"2022032516100827000_ref36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2022032516100827000_ref37","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res."},{"key":"2022032516100827000_ref38","first-page":"470","article-title":"Correlation between genetic structure and social class in Chile","volume":"113","author":"Cohn","year":"1985","journal-title":"Rev. Med. Chil."},{"key":"2022032516100827000_ref39","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4067\/S0716-97602011000400012","article-title":"Human sociogenetics","volume":"44","author":"Valenzuela","year":"2011","journal-title":"Biol. 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A."},{"key":"2022032516100827000_ref44","doi-asserted-by":"crossref","first-page":"eaau4921","DOI":"10.1126\/sciadv.aau4921","article-title":"The genetic prehistory of the Andean highlands 7000 years BP though European contact","volume":"4","author":"Lindo","year":"2018","journal-title":"Sci. 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