Blood donor biobank as a resource in personalised biomedical genetic research.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
12 Jan 2024
12 Jan 2024
Historique:
received:
30
05
2023
accepted:
19
12
2023
revised:
14
10
2023
medline:
12
1
2024
pubmed:
12
1
2024
entrez:
11
1
2024
Statut:
aheadofprint
Résumé
Health questionnaires and donation criteria result in accumulation of highly selected individuals in a blood donor population. To understand better the usefulness of a blood donor-based biobank in personalised disease-associated genetic studies, and for possible personalised blood donation policies, we evaluated the occurrence and distributions of common and rare disease-associated genetic variants in Finnish Blood Service Biobank. We analysed among 31,880 blood donors the occurrence and geographical distribution of (i) 53 rare Finnish-enriched disease-associated variants, (ii) mutations assumed to influence blood donation: four Bernard-Soulier syndrome and two hemochromatosis mutations, (iii) type I diabetes risk genotype HLA-DQ2/DQ8. In addition, we analysed the level of consanguinity in Blood Service Biobank. 80.3% of blood donors carried at least one (range 0-9 per donor) of the rare variants, many in homozygous form, as well. Donors carrying multiple rare variants were enriched in Eastern Finland. Haemochromatosis mutation HFE C282Y homozygosity was 43.8% higher than expected, whereas mutations leading to Bernard-Soulier thrombocytopenia were rare. The frequency of HLA-DQ2/DQ8 genotype was slightly lower than expected. First-degree consanguinity was higher in Blood Service Biobank than in the general population. We demonstrate that despite donor selection, the Blood Service Biobank is a valuable resource for personalised medical research and for genotype-selected samples from unaffected individuals. The geographical genetic substructure of Finland enables efficient recruitment of donors carrying rare variants. Furthermore, we show that blood donor biobank material can be utilised for personalised blood donation policies.
Identifiants
pubmed: 38212662
doi: 10.1038/s41431-023-01528-0
pii: 10.1038/s41431-023-01528-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Denny JC, Bastarache L, Ritchie MD, Carroll RJ, Zink R, Mosley JD, et al. A n a ly s i s Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data. Nat Biotechnol. 2013;31:1102–10.
doi: 10.1038/nbt.2749
pubmed: 24270849
pmcid: 3969265
Diogo D, Tian C, Franklin CS, Alanne-Kinnunen M, March M, Spencer CCA, et al. Population cohorts support drug target validation. Nat Commun. 2018;9:4285.1–13.
Mitchell R. Blood banks, biobanks, and the ethics of donation. Transfusion. 2010;50:1866–99.
doi: 10.1111/j.1537-2995.2010.02812.x
pubmed: 21050225
Raivola V, Snell K, Pastila S, Helén I, Partanen J. Blood donors’ preferences for blood donation for biomedical research. Transfusion. 2018;58:1640–6.
doi: 10.1111/trf.14596
pubmed: 29572859
Raivola V, Snell K, Helen I, Partanen J. Attitudes of blood donors to their sample and data donation for biobanking. Eur J Hum Genet. 2019;27:1659–67.
doi: 10.1038/s41431-019-0434-1
pubmed: 31147625
pmcid: 6871534
Atsma F, Veldhuizen I, Verbeek A, de Kort W, de Vegt F. Healthy donor effect: its magnitude in health research among blood donors. Transfusion. 2011;51:1820–8.
doi: 10.1111/j.1537-2995.2010.03055.x
pubmed: 21342203
Lim ET, Würtz P, Havulinna AS, Palta P, Tukiainen T, Rehnström K, et al. Distribution and medical impact of loss-of-function variants in the finnish founder population. PLoS Genet. 2014;10:e1004494.
doi: 10.1371/journal.pgen.1004494
pubmed: 25078778
pmcid: 4117444
Kere J. Human population genetics: lessons from Finland. Annu Rev Genom Hum Genet. 2001;2:103–28.
doi: 10.1146/annurev.genom.2.1.103
Norio R. Finnish Disease Heritage II: population prehistory and genetic roots of Finns. Hum Genet. 2003;112:457–69. http://link.springer.com/10.1007/s00439-002-0876-2
doi: 10.1007/s00439-002-0876-2
pubmed: 12627296
Norio R. The Finnish disease heritage III: the individual diseases. Hum Genet. 2003;112:470–526.
doi: 10.1007/s00439-002-0877-1
pubmed: 12627297
Sajantila A, Salem AH, Savolainen P, Bauer K, Gierig C, Paabo S. Paternal and maternal DNA lineages reveal a bottleneck in the founding of the Finnish population. Proc Natl Acad Sci USA. 1996;93:12035–9. http://www.pnas.org/cgi/doi/10.1073/pnas.93.21.12035
doi: 10.1073/pnas.93.21.12035
pubmed: 8876258
pmcid: 38178
Kerminen S, Havulinna AS, Hellenthal G, Martin AR, Sarin A-P, Perola M, et al. Fine-scale genetic structure in Finland. G3 Genes Genomes Genet. 2017;7:3459–68. https://academic.oup.com/g3journal/article/7/10/3459/6027487
doi: 10.1534/g3.117.300217
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner K, et al. FinnGen: unique genetic insights from combining isolated population and national health register data. Preprint at medRxiv. 2022. Available from: http://medrxiv.org/content/early/2022/03/06/2022.03.03.22271360.abstract
Koskela S, Javela K, Jouppila J, Juvonen E, Nyblom O, Partanen J, et al. Variant Bernard-Soulier syndrome due to homozygous Asn45Ser mutation in the platelet glycoprotein (GP) IX in seven patients of five unrelated Finnish families. Eur J Haematol. 1999;62:256–64.
doi: 10.1111/j.1600-0609.1999.tb01755.x
pubmed: 10227459
Koskela S, Partanen J, Salmi TT, Kekomäki R. Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families. Eur J Haematol. 1999;62:160–8.
doi: 10.1111/j.1600-0609.1999.tb01739.x
pubmed: 10089893
FinnGen. FinnGen Documentation of data release [Internet]. 2022. Available from: https://finngen.gitbook.io/documentation/
Savoia A, Kunishima S, De Rocco D, Zieger B, Rand ML, Pujol-Moix N, et al. Spectrum of the mutations in Bernard–Soulier syndrome. Hum Mutat. 2014;35:1033–45. https://doi.org/10.1002/humu.22607 .
doi: 10.1002/humu.22607
pubmed: 24934643
Hu X, Deutsch AJ, Lenz TL, Onengut-Gumuscu S, Han B, Chen W-M, et al. Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk. Nat Genet. 2015;47:898–905.
doi: 10.1038/ng.3353
pubmed: 26168013
pmcid: 4930791
Thomson G, Robinson WP, Kuhner MK, Joe S, MacDonald MJ, Gottschall JL, et al. Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet. 1988;43:799–816.
pubmed: 3057885
pmcid: 1715606
Zheng X, Shen J, Cox C, Wakefield JC, Ehm MG, Nelson MR, et al. HIBAG - HLA genotype imputation with attribute bagging. Pharmacogenomics J. 2014;14:192–200.
doi: 10.1038/tpj.2013.18
pubmed: 23712092
Ritari J, Hyvärinen K, Clancy J, FinnGen, Partanen J, Koskela S. Increasing accuracy of HLA imputation by a population-specific reference panel in a FinnGen biobank cohort. NAR Genom Bioinform. 2020;2:lqaa030.
doi: 10.1093/nargab/lqaa030
pubmed: 33575586
pmcid: 7671345
Linjama T, Räther C, Ritari J, Peräsaari J, Eberhard H-P, Korhonen M, et al. Extended HLA haplotypes and their impact on DPB1 matching of unrelated hematologic stem cell transplant donors. Biol Blood Marrow Transpl. 2019;25:1956–64. https://linkinghub.elsevier.com/retrieve/pii/S1083879119304409
doi: 10.1016/j.bbmt.2019.07.008
R Core Team [Internet]. Available from: https://www.r-project.org/
R studio [Internet]. Available from: https://www.rstudio.com/
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434–43. https://doi.org/10.1038/s41586-020-2308-7 .
doi: 10.1038/s41586-020-2308-7
pubmed: 32461654
pmcid: 7334197
gnomAD Genome Aggregation Database [Internet]. Available from: https://gnomad.broadinstitute.org/
Simon M, Le Mignon L, Fauchet R, Yaouanq J, David V, Edan G, et al. A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association. Am J Hum Genet. 1987;41:89–105.
pubmed: 3475981
pmcid: 1684230
Simon M, Bourel M, Fauchet R, Genetet B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut. 1976;17:332 LP–334. http://gut.bmj.com/content/17/5/332.abstract
doi: 10.1136/gut.17.5.332
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613:508–18.
doi: 10.1038/s41586-022-05473-8
pubmed: 36653562
pmcid: 9849126
Atsma F, De Vegt F. The healthy donor effect: a matter of selection bias and confounding. Transfusion. 2011;51:1883–5.
doi: 10.1111/j.1537-2995.2011.03270.x
pubmed: 21790637
Peltonen L, Jalanko A, Varilo T. Molecular genetics of the Finnish disease heritage. Hum Mol Genet. 1999;8:1913–23.
doi: 10.1093/hmg/8.10.1913
pubmed: 10469845
Norio R. Finnish Disease Heritage II: population prehistory and genetic roots of Finns. Hum Genet. 2003;112:457–69.
doi: 10.1007/s00439-002-0876-2
pubmed: 12627296
Salmela E, Lappalainen T, Fransson I, Andersen PM, Dahlman-Wright K, Fiebig A, et al. Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe. PLoS ONE. 2008;3:e3519.
doi: 10.1371/journal.pone.0003519
pubmed: 18949038
pmcid: 2567036
Wartiovaara U, Perola M, Mikkola H, Tötterman K, Savolainen V, Penttilä A, et al. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males. Atherosclerosis. 1999;142:295–300.
doi: 10.1016/S0021-9150(98)00241-X
pubmed: 10030380
Palo JU, Ulmanen I, Lukka M, Ellonen P, Sajantila A. Genetic markers and population history: Finland revisited. Eur J Hum Genet. 2009;17:1336–46.
doi: 10.1038/ejhg.2009.53
pubmed: 19367325
pmcid: 2986642
Symonette CJ, Adams PC. Do all hemochromatosis patients have the same origin? An analysis of mitochondrial DNA and Y-DNA. Can J Gastroenterol. 2011;25:324–6.
doi: 10.1155/2011/463810
pubmed: 21766093
pmcid: 3142605
Olsson KS, Ritter B, Raha-Chowdhury R. HLA-A3-B14 and the origin of the haemochromatosis C282Y mutation: founder effects and recombination events during 12 generations in a Scandinavian family with major iron overload. Eur J Haematol. 2010;84:145–53.
doi: 10.1111/j.1600-0609.2009.01376.x
pubmed: 19912313
Reuben A, Chung JW, Lapointe R, Santos MM. The hemochromatosis protein HFE 20 years later: an emerging role in antigen presentation and in the immune system. Immun Inflamm Dis. 2017;5:218–32.
doi: 10.1002/iid3.158
pubmed: 28474781
pmcid: 5569368
Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta. 2006;1763:700–10.
doi: 10.1016/j.bbamcr.2006.05.013
pubmed: 16891003
Brissot P, Pietrangelo A, Adams PC, de Graaff B, McLaren CE, Loréal O. Haemochromatosis. Nat Rev Dis Prim. 2018;4:18016.
doi: 10.1038/nrdp.2018.16
pubmed: 29620054
Mantadakis E, Panagopoulou P, Kontekaki E, Bezirgiannidou Z, Martinis G. Iron deficiency and blood donation: links, risks and management. J Blood Med. 2022;13:775–86.
doi: 10.2147/JBM.S375945
pubmed: 36531435
pmcid: 9749410
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol. 2022;77:479–502.
Miller DT, Lee K, Chung WK, Gordon AS, Herman GE, Klein TE, et al. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23:1381–90.
doi: 10.1038/s41436-021-01172-3
pubmed: 34012068
López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood. 1998;91:4397–418.
doi: 10.1182/blood.V91.12.4397
pubmed: 9616133
Sojka BN, Sojka P. The blood donation experience: self-reported motives and obstacles for donating blood. Vox Sang. 2008;94:56–63.
doi: 10.1111/j.1423-0410.2007.00990.x
pubmed: 18171329
Quéniart A. Blood donation within the family: the transmission of values and practices. Transfusion. 2013;53 Suppl 5:151S–6S.
pubmed: 24341427