Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations

• Published in: Scientific reports 2022-01, Vol.12 (1), p.1131-13, Article 1131
• Main Authors: Kuchenbaecker, Karoline, Gilly, Arthur, Suveges, Daniel, Southam, Lorraine, Giannakopoulou, Olga, Kilian, Britt, Tsafantakis, Emmanouil, Karaleftheri, Maria, Farmaki, Aliki-Eleni, Gurdasani, Deepti, Kundu, Kousik, Sandhu, Manjinder S., Danesh, John, Butterworth, Adam, Barroso, Inês, Dedoussis, George, Zeggini, Eleftheria
• Format: Article
• Language: English
• Subjects: 631/208/205; 631/208/212/2301; 631/208/480; 631/208/514/1948; 631/208/514/2254; 692/53; Alleles; beta-Globins - genetics; Bilirubin; Cholesterol; Cohort Studies; DNA Mutational Analysis; Erythrocyte Count; Erythrocyte Indices - genetics; Erythrocytes; Gene Frequency; Genetic diversity; Genetic Variation; Genetics, Population; Genome-Wide Association Study; Genomes; Greece; Hematology; Hemoglobin; Humanities and Social Sciences; Humans; Leukocyte Count; multidisciplinary; Mutation; Phenotyping; Platelet Function Tests; Population genetics; Science; Science (multidisciplinary); Whole Genome Sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-04436-9

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 ( p  A) (rs35004220). In the Pomak population, c.364C>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>C) compared to other b+ mutations. Overall, we uncover allelic diversity of HBB in Greek isolated populations and find an important role for additional rare variants outside of HBB .