Show simple item record

dc.contributor.authorKuchenbaecker, Karoline
dc.contributor.authorGilly, Arthur
dc.contributor.authorSuveges, Daniel
dc.contributor.authorSoutham, Lorraine
dc.contributor.authorGiannakopoulou, Olga
dc.contributor.authorKilian, Britt
dc.contributor.authorTsafantakis, Emmanouil
dc.contributor.authorKaraleftheri, Maria
dc.contributor.authorFarmaki, Aliki-Eleni
dc.contributor.authorGurdasani, Deepti
dc.contributor.authorKundu, Kousik
dc.contributor.authorSandhu, Manjinder S
dc.contributor.authorDanesh, John
dc.contributor.authorButterworth, Adam
dc.contributor.authorBarroso, Inês
dc.contributor.authorDedoussis, George
dc.contributor.authorZeggini, Eleftheria
dc.date.accessioned2022-01-21T00:30:36Z
dc.date.available2022-01-21T00:30:36Z
dc.date.issued2022-12
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332818
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>Haematological traits are linked to cardiovascular, metabolic, infectious and immune disorders, as well as cancer. Here, we examine the role of genetic variation in shaping haematological traits in two isolated Mediterranean populations. Using whole-genome sequencing data at 22× depth for 1457 individuals from Crete (MANOLIS) and 1617 from the Pomak villages in Greece, we carry out a genome-wide association scan for haematological traits using linear mixed models. We discover novel associations (<jats:italic>p</jats:italic> &lt; 5 × 10<jats:sup>–9</jats:sup>) of five rare non-coding variants with alleles conferring effects of 1.44–2.63 units of standard deviation on red and white blood cell count, platelet and red cell distribution width. Moreover, 10.0% of individuals in the Pomak population and 6.8% in MANOLIS carry a pathogenic mutation in the Haemoglobin Subunit Beta (HBB) gene. The mutational spectrum is highly diverse (10 different mutations). The most frequent mutation in MANOLIS is the common Mediterranean variant IVS-I-110 (G&gt;A) (rs35004220). In the Pomak population, c.364C&gt;A (“HbO-Arab”, rs33946267) is most frequent (4.4% allele frequency). We demonstrate effects on haematological and other traits, including bilirubin, cholesterol, and, in MANOLIS, height and gestation age. We find less severe effects on red blood cell traits for HbS, HbO, and IVS-I-6 (T&gt;C) compared to other b+ mutations. Overall, we uncover allelic diversity of <jats:italic>HBB</jats:italic> in Greek isolated populations and find an important role for additional rare variants outside of <jats:italic>HBB</jats:italic>.</jats:p>
dc.description.sponsorshipEuropean Research Council (ERC-2011-StG 280559-SEPI).
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleInsights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations
dc.typeArticle
dc.date.updated2022-01-19T14:56:10Z
prism.publicationNameScientific Reports
dc.identifier.doi10.17863/CAM.80252
dcterms.dateAccepted2022-01-18
rioxxterms.versionofrecord10.1038/s41598-021-04436-9
rioxxterms.versionVoR
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
cam.issuedOnline2022-01-21
cam.orpheus.success2022-01-20 - Embargo set during processing via Fast-track
cam.depositDate2022-01-19
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2100-01-01


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International