Evidence of Polygenic Adaptation in Sardinia at Height-Associated Loci Ascertained from the Biobank Japan
Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus re...
Gespeichert in:
| Veröffentlicht in: | American journal of human genetics Jg. 107; H. 1; S. 60 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
02.07.2020
|
| Schlagworte: | |
| ISSN: | 1537-6605, 1537-6605 |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10
). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10
). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis. |
|---|---|
| AbstractList | Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10
). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10
). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis. Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10-4). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10-4). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10-4). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10-4). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis. |
| Author | Cucca, Francesco Okada, Yukinori Ishigaki, Kazuyoshi Akiyama, Masato Schlessinger, David Sidore, Carlo Kamatani, Yoichiro Chiang, Charleston W K Chen, Minhui |
| Author_xml | – sequence: 1 givenname: Minhui surname: Chen fullname: Chen, Minhui email: minhuic@usc.edu organization: Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: minhuic@usc.edu – sequence: 2 givenname: Carlo surname: Sidore fullname: Sidore, Carlo organization: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato 09042, Cagliari, Italy – sequence: 3 givenname: Masato surname: Akiyama fullname: Akiyama, Masato organization: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan – sequence: 4 givenname: Kazuyoshi surname: Ishigaki fullname: Ishigaki, Kazuyoshi organization: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan – sequence: 5 givenname: Yoichiro surname: Kamatani fullname: Kamatani, Yoichiro organization: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan – sequence: 6 givenname: David surname: Schlessinger fullname: Schlessinger, David organization: Laboratory of Genetics and Genomics, National Institute on Aging, US National Institutes of Health, Baltimore, MD 21224, USA – sequence: 7 givenname: Francesco surname: Cucca fullname: Cucca, Francesco organization: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato 09042, Cagliari, Italy – sequence: 8 givenname: Yukinori surname: Okada fullname: Okada, Yukinori organization: Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan – sequence: 9 givenname: Charleston W K surname: Chiang fullname: Chiang, Charleston W K email: charleston.chiang@med.usc.edu organization: Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Quantitative and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: charleston.chiang@med.usc.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32533944$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkE1Lw0AYhBep2A_9Ax5kj14S9yObj2Mt1SoFBfUc3mzebbcmuzXZCv33BqzgaYbhYRhmSkbOOyTkmrOYM57e7WLYbTexYILFTMWMJ2dkwpXMojRlavTPj8m073eMcZ4zeUHGUigpiySZELv8tjU6jdQb-uqb4wad1XRewz5AsN5R6-gbdLV1FigEukK72YZo3vdeWwhY0_Vg6LzX2AWwbghM51satkjvra_AfdJn2IO7JOcGmh6vTjojHw_L98UqWr88Pi3m60grwUOUKJOjAChMApDVskDBNVQJiixnpkLGap5Uqc4yo4rcoDYi55plCmRuCqnFjNz-9u47_3XAPpStHcY1DTj0h74UCRdFnkqVD-jNCT1ULdblvrMtdMfy7x7xA75napg |
| CitedBy_id | crossref_primary_10_1016_j_ajhg_2022_12_011 crossref_primary_10_1016_j_gde_2020_06_003 crossref_primary_10_1007_s00439_021_02281_4 crossref_primary_10_1093_bib_bbac354 crossref_primary_10_1038_s41431_021_00938_2 crossref_primary_10_1038_s41586_023_06705_1 crossref_primary_10_1093_genetics_iyaf071 crossref_primary_10_1016_j_ajhg_2025_05_009 crossref_primary_10_1038_s41562_021_01231_4 crossref_primary_10_1016_j_ajhg_2021_02_011 crossref_primary_10_1016_j_ajhg_2021_07_003 crossref_primary_10_1007_s00438_024_02172_z crossref_primary_10_1038_s41586_025_08998_w crossref_primary_10_1038_s41588_022_01062_7 crossref_primary_10_1016_j_cub_2023_08_021 crossref_primary_10_3389_fgene_2021_703541 |
| ContentType | Journal Article |
| Copyright | Copyright © 2020 American Society of Human Genetics. All rights reserved. |
| Copyright_xml | – notice: Copyright © 2020 American Society of Human Genetics. All rights reserved. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.ajhg.2020.05.014 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1537-6605 |
| ExternalDocumentID | 32533944 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GeographicLocations | Italy Japan |
| GeographicLocations_xml | – name: Italy – name: Japan |
| GrantInformation_xml | – fundername: NIDA NIH HHS grantid: HHSN271201100005C |
| GroupedDBID | --- --K --Z -~X 0R~ 123 1~5 23M 2WC 4.4 457 4G. 53G 5GY 62- 6J9 7-5 85S AAEDT AAEDW AAFWJ AAKRW AALRI AAMRU AAVLU AAWTL AAXUO ABDGV ABJNI ABMAC ABOCM ACGFO ACGFS ACGOD ACNCT ACPRK ACVFH ADBBV ADCNI ADEZE ADVLN AENEX AEUPX AEXQZ AFPUW AFRAH AFTJW AGCQF AGKMS AHMBA AIGII AITUG AKAPO AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ AOIJS APXCP ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF D0L DIK E3Z EBS ECM ECV EFKBS EIF F5P FCP FDB FEDTE GX1 HVGLF HYE IH2 IHE IXB JIG KQ8 L7B M41 NPM O-L O9- OK1 P2P PQQKQ RNS ROL RPM RPZ SES SJN SSZ TN5 TR2 TWZ UHB UKR UNMZH UPT WH7 ZCA 7X8 |
| ID | FETCH-LOGICAL-c521t-45f8e2aa9f4aa7d39e21cab4e2780fbe00d14b6c77f598fecf281c075a38f93c2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 20 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000546685300006&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1537-6605 |
| IngestDate | Sun Sep 28 10:50:13 EDT 2025 Mon Jul 21 05:50:53 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | population stratification polygenic adaptation height |
| Language | English |
| License | Copyright © 2020 American Society of Human Genetics. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c521t-45f8e2aa9f4aa7d39e21cab4e2780fbe00d14b6c77f598fecf281c075a38f93c2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://www.cell.com/article/S0002929720301610/pdf |
| PMID | 32533944 |
| PQID | 2412986358 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2412986358 pubmed_primary_32533944 |
| PublicationCentury | 2000 |
| PublicationDate | 2020-07-02 |
| PublicationDateYYYYMMDD | 2020-07-02 |
| PublicationDate_xml | – month: 07 year: 2020 text: 2020-07-02 day: 02 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | American journal of human genetics |
| PublicationTitleAlternate | Am J Hum Genet |
| PublicationYear | 2020 |
| SSID | ssj0011803 |
| Score | 2.4358795 |
| Snippet | Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 60 |
| SubjectTerms | Adaptation, Physiological - genetics Alleles Asian People - genetics Biological Specimen Banks Body Height - genetics Genetics, Population - methods Genome, Human - genetics Genome-Wide Association Study - methods Haplotypes - genetics Humans Italy Japan Multifactorial Inheritance - genetics Phenotype Polymorphism, Single Nucleotide - genetics Selection, Genetic - genetics White People - genetics |
| Title | Evidence of Polygenic Adaptation in Sardinia at Height-Associated Loci Ascertained from the Biobank Japan |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32533944 https://www.proquest.com/docview/2412986358 |
| Volume | 107 |
| WOSCitedRecordID | wos000546685300006&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qKnjx_VhfRPBabJN0k5xkEZdFdFlQYW8lzUOr0q52FfbfO-mDPQmCl1IKpSXzTeZLZjIfQhfGRc5wJgIK3DVgzoBLSRP6vrfOOIggXKeV2AQfjcRkIsfNhlvZlFW2c2I1UZtC-z3yS4g0RAoIj-Jq-hF41SifXW0kNJZRhwKV8ajmk0UWIRKVMjI4NQ96wNubQzN1fZd6fXmG9SEJ686d7HeKWYWaweZ_f3ILbTQkE_drVGyjJZvvoLVadnK-i7JWShQXDo-L9zmAKNO4b9S0TszjLMcPHjp5prCa4WG1fxq0prQG38EN7pe6LiiAB_6YCgYyieErqcrf8C1E4XwPPQ1uHq-HQSO5EGivbBCw2AlLlJKOKcUNlZZEWqXMEi5Cl9owNBFLe5pzF0vhrHZERBpoh6LCSarJPlrJi9weIkypAnIieMp6gmkeylQCG9SMWQHrvjjuovN2DBOAtM9TqNwWX2WyGMUuOqgNkUzr3hsJJcBPJWNHf3j7GK17-1bFteQEdRw4tD1Fq_p7lpWfZxVW4Doa3_8A_P_Iew |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Evidence+of+Polygenic+Adaptation+in+Sardinia+at+Height-Associated+Loci+Ascertained+from+the+Biobank+Japan&rft.jtitle=American+journal+of+human+genetics&rft.au=Chen%2C+Minhui&rft.au=Sidore%2C+Carlo&rft.au=Akiyama%2C+Masato&rft.au=Ishigaki%2C+Kazuyoshi&rft.date=2020-07-02&rft.issn=1537-6605&rft.eissn=1537-6605&rft.volume=107&rft.issue=1&rft.spage=60&rft_id=info:doi/10.1016%2Fj.ajhg.2020.05.014&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1537-6605&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1537-6605&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1537-6605&client=summon |