Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Los estudios de asociación de todo el genoma y la edición de genes mediada por CRISPR/Cas9 identifican variantes reguladoras que influyen en el grosor de las cejas en humanos

dc.contributorzhangliang01@sibs.ac.cn; lijin@fudan.edu.cn; wangsijia@picb.ac.cn
dc.contributorStrategic Priority Research Program of the Chinese Academy of Sciences [XDB13041000]; Science and Technology Commission of Shanghai Municipality [16JC1400504]; National Natural Science Foundation of China (NSFC) grant [91631307, 30890034, 31271338, 31471385, 81673104, 91731303, 31771388, 31525014, 31711530221]; National Thousand Young Talents Award; Max Planck-CAS Paul Gerson Unna Independent Research Group Leadership Award; National Basic Research Program [2015FY111700]; Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]; Ministry of Education [311016]; Chinese Academy of Sciences [XDB13040100]; Program of Shanghai Academic Research Leader [16XD1404700]; National Key Research and Development Program [216YFC0906403]; National Key R&D Program of China [2017YFA0103500, 2017YFA0102800]; Shanghai Science and Technology Development Funds [15140904200]; National Program for Top-notch Young Innovative Talents of The Wanren Jihua Project; Leverhulme Trust [F/07 134/DF]; BBSRC [BB/1021213/1]; Institute Strategic Programme grant; Universidad de Antioquia; Erasmus University Rotterdam (EUR) fellowship; Chinese 1000-Talentss Program; Vidi Grant of the Netherlands Organization Organization for the Health Research and Development (ZonMw) [91711315]; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Chinese 1000-Talents Program; Vidi Grant of the Netherlands Organization for the Health Research and Development (ZonMw) [91711315]; Netherlands Organization of Scientific Research NWO Investments; BBSRC [BB/I021213/1] Funding Source: UKRI
dc.contributorXu, Shuhua https://orcid.org/0000-0002-1975-1002
dc.contributorSCHULER-FACCINI, LAVINIA https://orcid.org/0000-0002-2428-0460
dc.contributorLi, Jinxi https://orcid.org/0000-0002-1366-9593
dc.contributorJin, Li https://orcid.org/0000-0002-4546-2415
dc.contributorPeng, Fuduan https://orcid.org/0000-0003-4068-530X
dc.contributorRuiz-Linares, Andres https://orcid.org/0000-0001-8372-1011
dc.contributorPeng, Qianqian https://orcid.org/0000-0002-2018-5706
dc.contributorLiu, Fan https://orcid.org/0000-0001-9241-8161
dc.contributorZhang, Liang https://orcid.org/0000-0003-4396-9199
dc.contributorJin, Li https://orcid.org/0000-0001-9201-2321
dc.creatorWu, Sijie
dc.creatorZhang, Manfei
dc.creatorYang, Xinzhou
dc.creatorPeng, Fuduan
dc.creatorZhang, Juan
dc.creatorTan, Jingze
dc.creatorYang, Yajun
dc.creatorWang, Lina
dc.creatorHu, Yanan
dc.creatorPeng, Qianqian
dc.creatorLi, Jinxi
dc.creatorLiu, Yu
dc.creatorGuan, Yaqun
dc.creatorChen, Chen
dc.creatorHamer, Merel A.
dc.creatorNijsten, Tamar
dc.creatorZeng, Changqing
dc.creatorAdhikari, Kaustubh
dc.creatorGallo, Carla
dc.creatorPoletti, Giovanni
dc.creatorSchuler-Faccini, Lavinia
dc.creatorBortolini, Maria-Catira
dc.creatorCanizales-Quinteros, Samuel
dc.creatorRothhammer, Francisco
dc.creatorBedoya, Gabriel
dc.creatorGonzalez-Jose, Rolando
dc.creatorLi, Hui
dc.creatorKrutmann, Jean
dc.creatorLiu, Fan
dc.creatorKayser, Manfred
dc.creatorRuiz-Linares, Andres
dc.creatorTang, Kun
dc.creatorXu, Shuhua
dc.creatorZhang, Liang
dc.creatorJin, Li
dc.creatorWang, Sijia
dc.date2023-04-18T01:55:32Z
dc.date2023-04-18T01:55:32Z
dc.date2018
dc.date.accessioned2023-09-27T20:20:07Z
dc.date.available2023-09-27T20:20:07Z
dc.identifier1553-7404
dc.identifierhttps://repositorio.uta.cl/xmlui/handle/20.500.14396/2800
dc.identifier10.1371/journal.pgen.1007640
dc.identifierGV5QO
dc.identifier30248107
dc.identifierWOS:000446157400023
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8943385
dc.descriptionHair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51x10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73x10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81x10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.
dc.descriptionEl pelo juega un papel importante en los primates y está claramente sujeto a la selección adaptativa. Si bien los humanos han perdido la mayor parte del vello facial, las cejas son una notable excepción. El grosor de las cejas es hereditario y se cree ampliamente que está sujeto a selección sexual. Sin embargo, pocos estudios genómicos han explorado su base genética. Aquí, realizamos un escaneo de todo el genoma para el grosor de las cejas en 2961 Han Chinese. Identificamos dos nuevos loci de importancia en todo el genoma, en 3q26.33 cerca de SOX2 (rs1345417: P = 6.51x10 (-10)) y en 5q13.2 cerca de FOXD1 (rs12651896: P = 1.73x10 (-8)). Repetimos aún más nuestros hallazgos en los uigures, una población de China caracterizada por una mezcla de Asia oriental y Europa (N = 721), la cohorte CANDELA de cinco países latinoamericanos (N = 2301) y la cohorte del estudio de Rotterdam de europeos holandeses (N = 4411). Un metanálisis que combinó los resultados completos de GWAS de las tres cohortes de ascendencia asiática total o parcial (chinos Han, uigures y latinoamericanos, N = 5983) destacó una tercera señal de importancia en todo el genoma en 2q12.3 (rs1866188: P = 5.81x10(-11)) cerca de EDAR. Realizamos un mapeo fino y priorizamos cuatro variantes para una verificación experimental adicional. La edición de genes mediada por CRISPR/Cas9 proporcionó evidencia de que rs1345417 y rs12651896 afectan la actividad transcripcional de los genes cercanos SOX2 y FOXD1, que están involucrados en el desarrollo del cabello. Finalmente, los análisis estadísticos adecuados revelaron que ninguna de las variantes asociadas mostró señales claras de selección en ninguna de las poblaciones probadas. Contrariamente a la especulación popular, no encontramos evidencia de que el grosor de las cejas esté sujeto a una fuerte presión selectiva.
dc.formatapplication/pdf
dc.format22 páginas
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relationPlos Genetics, vol.14 no.9 (2018)
dc.relationhttps://doi.org/10.1371/journal.pgen.1007640
dc.rightsGreen Accepted, Green Submitted, gold, Green Published
dc.rightsAcceso abierto
dc.sourcePlos Genetics
dc.subjectPositive Selection
dc.subjectHair
dc.subjectExpression
dc.subjectTranscriptome
dc.subjectMetaanalysis
dc.subjectEdarv370a
dc.subjectRotterdam
dc.subjectAndrogens
dc.subjectEvolution
dc.subjectAmericans
dc.subjectSelección Positiva
dc.subjectCabello
dc.subjectExpresión
dc.subjectTranscriptoma
dc.subjectMetaanálisis
dc.subjectEdarv370a
dc.subjectRotterdam
dc.subjectAndrógenos
dc.subjectEvolución
dc.subjectAmericanos
dc.titleGenome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans
dc.titleLos estudios de asociación de todo el genoma y la edición de genes mediada por CRISPR/Cas9 identifican variantes reguladoras que influyen en el grosor de las cejas en humanos
dc.typeArtículo de revista


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