30 results on '"Eyjolfsson, Gudmundur I."'
Search Results
2. Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets
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Grarup, Niels, Sulem, Patrick, Sandholt, Camilla H, Thorleifsson, Gudmar, Ahluwalia, Tarunveer S, Steinthorsdottir, Valgerdur, Bjarnason, Helgi, Gudbjartsson, Daniel F, Magnusson, Olafur T, Sparsø, Thomas, Albrechtsen, Anders, Kong, Augustine, Masson, Gisli, Tian, Geng, Cao, Hongzhi, Nie, Chao, Kristiansen, Karsten, Husemoen, Lise Lotte, Thuesen, Betina, Li, Yingrui, Nielsen, Rasmus, Linneberg, Allan, Olafsson, Isleifur, Eyjolfsson, Gudmundur I, Jørgensen, Torben, Wang, Jun, Hansen, Torben, Thorsteinsdottir, Unnur, Stefánsson, Kari, and Pedersen, Oluf
- Subjects
Biotechnology ,Prevention ,Human Genome ,Genetics ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Alzheimer Disease ,Denmark ,Exome ,Folic Acid ,Folic Acid Deficiency ,Genome ,Human ,Genome-Wide Association Study ,Humans ,Iceland ,Methylenetetrahydrofolate Reductase (NADPH2) ,Quantitative Trait Loci ,Vitamin B 12 ,Developmental Biology - Abstract
Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.
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- 2013
3. Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis
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Olafsdottir, Thorunn A., Theodors, Fannar, Bjarnadottir, Kristbjorg, Bjornsdottir, Unnur Steina, Agustsdottir, Arna B., Stefansson, Olafur A., Ivarsdottir, Erna V., Sigurdsson, Jon K., Benonisdottir, Stefania, Eyjolfsson, Gudmundur I., Gislason, David, Gislason, Thorarinn, Guðmundsdóttir, Steinunn, Gylfason, Arnaldur, Halldorsson, Bjarni V., Halldorsson, Gisli H., Juliusdottir, Thorhildur, Kristinsdottir, Anna M., Ludviksdottir, Dora, Ludviksson, Bjorn R., Masson, Gisli, Norland, Kristjan, Onundarson, Pall T., Olafsson, Isleifur, Sigurdardottir, Olof, Stefansdottir, Lilja, Sveinbjornsson, Gardar, Tragante, Vinicius, Gudbjartsson, Daniel F., Thorleifsson, Gudmar, Sulem, Patrick, Thorsteinsdottir, Unnur, Norddahl, Gudmundur L., Jonsdottir, Ingileif, and Stefansson, Kari
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- 2020
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4. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease
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Ferkingstad, Egil, Oddsson, Asmundur, Gretarsdottir, Solveig, Benonisdottir, Stefania, Thorleifsson, Gudmar, Deaton, Aimee M., Jonsson, Stefan, Stefansson, Olafur A., Norddahl, Gudmundur L., Zink, Florian, Arnadottir, Gudny A., Gunnarsson, Bjarni, Halldorsson, Gisli H., Helgadottir, Anna, Jensson, Brynjar O., Kristjansson, Ragnar P., Sveinbjornsson, Gardar, Sverrisson, David A., Masson, Gisli, Olafsson, Isleifur, Eyjolfsson, Gudmundur I., Sigurdardottir, Olof, Holm, Hilma, Jonsdottir, Ingileif, Olafsson, Sigurdur, Steingrimsdottir, Thora, Rafnar, Thorunn, Bjornsson, Einar S., Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., Sulem, Patrick, and Stefansson, Kari
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- 2018
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5. A rare missense variant in NR1H4 associates with lower cholesterol levels
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Deaton, Aimee M., Sulem, Patrick, Nioi, Paul, Benonisdottir, Stefania, Ward, Lucas D., Davidsson, Olafur B., Lao, Socheata, Helgadottir, Anna, Fan, Fan, Jensson, Brynjar O., Norddahl, Gudmundur L., Jonasdottir, Aslaug, Jonasdottir, Adalbjorg, Sigurdsson, Asgeir, Kristjansson, Ragnar P., Oddsson, Asmundur, Arnadottir, Gudny A., Jonsson, Hakon, Olafsson, Isleifur, Eyjolfsson, Gudmundur I., Sigurdardottir, Olof, Bjornsson, Einar S., Olafsson, Sigurdur, Steingrimsdottir, Thora, Rafnar, Thorunn, Thorgeirsson, Gudmundur, Masson, Gisli, Thorleifsson, Gudmar, Gudbjartsson, Daniel F., Holm, Hilma, Thorsteinsdottir, Unnur, and Stefansson, Kari
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- 2018
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6. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits
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Styrkarsdottir, Unnur, Thorleifsson, Gudmar, Sulem, Patrick, Gudbjartsson, Daniel F., Sigurdsson, Asgeir, Jonasdottir, Aslaug, Jonasdottir, Adalbjorg, Oddsson, Asmundur, Helgason, Agnar, Magnusson, Olafur T., Walters, G. Bragi, Frigge, Michael L., Helgadottir, Hafdis T., Johannsdottir, Hrefna, Bergsteinsdottir, Kristin, Ogmundsdottir, Margret H., Center, Jacqueline R., Nguyen, Tuan V., Eisman, John A., Christiansen, Claus, Steingrimsson, Erikur, Jonasson, Jon G., Tryggvadottir, Laufey, Eyjolfsson, Gudmundur I., Theodors, Asgeir, Jonsson, Thorvaldur, Ingvarsson, Thorvaldur, Olafsson, Isleifur, Rafnar, Thorunn, Kong, Augustine, Sigurdsson, Gunnar, Masson, Gisli, Thorsteinsdottir, Unnur, and Stefansson, Kari
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- 2013
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7. Lifelong Reduction in LDL (Low-Density Lipoprotein) Cholesterol due to a Gain-of-Function Mutation in LDLR
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Bjornsson, Eythor, primary, Gunnarsdottir, Kristbjorg, additional, Halldorsson, Gisli H., additional, Sigurdsson, Asgeir, additional, Arnadottir, Gudny A., additional, Jonsson, Hakon, additional, Olafsdottir, Eva F., additional, Niehus, Sebastian, additional, Kehr, Birte, additional, Sveinbjörnsson, Gardar, additional, Gudmundsdottir, Steinunn, additional, Helgadottir, Anna, additional, Andersen, Karl, additional, Thorleifsson, Gudmar, additional, Eyjolfsson, Gudmundur I., additional, Olafsson, Isleifur, additional, Sigurdardottir, Olof, additional, Saemundsdottir, Jona, additional, Jonsdottir, Ingileif, additional, Magnusson, Olafur Th., additional, Masson, Gisli, additional, Stefansson, Hreinn, additional, Gudbjartsson, Daniel F., additional, Thorgeirsson, Gudmundur, additional, Holm, Hilma, additional, Halldorsson, Bjarni V., additional, Melsted, Pall, additional, Norddahl, Gudmundur L., additional, Sulem, Patrick, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional
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- 2021
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8. Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood
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Olafsson, Sigurgeir, primary, Alexandersson, Kristjan F., additional, Gizurarson, Johann G.K., additional, Hauksdottir, Katrin, additional, Gunnarsson, Orvar, additional, Olafsson, Karl, additional, Gudmundsson, Julius, additional, Stacey, Simon N., additional, Sveinbjornsson, Gardar, additional, Saemundsdottir, Jona, additional, Bjornsson, Einar S., additional, Olafsson, Sigurdur, additional, Bjornsson, Sigurdur, additional, Orvar, Kjartan B., additional, Vikingsson, Arnor, additional, Geirsson, Arni J., additional, Arinbjarnarson, Sturla, additional, Bjornsdottir, Gyda, additional, Thorgeirsson, Thorgeir E., additional, Sigurdsson, Snaevar, additional, Halldorsson, Gisli H., additional, Magnusson, Olafur T., additional, Masson, Gisli, additional, Holm, Hilma, additional, Jonsdottir, Ingileif, additional, Sigurdardottir, Olof, additional, Eyjolfsson, Gudmundur I., additional, Olafsson, Isleifur, additional, Sulem, Patrick, additional, Thorsteinsdottir, Unnur, additional, Jonsson, Thorvaldur, additional, Rafnar, Thorunn, additional, Gudbjartsson, Daniel F., additional, and Stefansson, Kari, additional
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- 2020
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9. Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes
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Gudbjartsson, Daniel F., primary, Thorgeirsson, Gudmundur, additional, Sulem, Patrick, additional, Helgadottir, Anna, additional, Gylfason, Arnaldur, additional, Saemundsdottir, Jona, additional, Bjornsson, Eythor, additional, Norddahl, Gudmundur L., additional, Jonasdottir, Aslaug, additional, Jonasdottir, Adalbjorg, additional, Eggertsson, Hannes P., additional, Gretarsdottir, Solveig, additional, Thorleifsson, Gudmar, additional, Indridason, Olafur S., additional, Palsson, Runolfur, additional, Jonasson, Fridbert, additional, Jonsdottir, Ingileif, additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Olafsson, Isleifur, additional, Danielsen, Ragnar, additional, Matthiasson, Stefan E., additional, Kristmundsdottir, Snaedis, additional, Halldorsson, Bjarni V., additional, Hreidarsson, Astradur B., additional, Valdimarsson, Einar M., additional, Gudnason, Thorarinn, additional, Benediktsson, Rafn, additional, Steinthorsdottir, Valgerdur, additional, Thorsteinsdottir, Unnur, additional, Holm, Hilma, additional, and Stefansson, Kari, additional
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- 2019
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10. Sequence variants associating with urinary biomarkers
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Onderzoek Precision medicine, Circulatory Health, Team Medisch, Benonisdottir, Stefania, Kristjansson, Ragnar P, Oddsson, Asmundur, Steinthorsdottir, Valgerdur, Mikaelsdottir, Evgenia, Kehr, Birte, Jensson, Brynjar O, Arnadottir, Gudny A, Sulem, Gerald, Sveinbjornsson, Gardar, Kristmundsdottir, Snaedis, Ivarsdottir, Erna V, Vogel, Lotte K, Tragante, Vinicius, Gunnarsson, Bjarni, Runolfsdottir, Hrafnhildur Linnet, Arthur, Joseph G, Deaton, Aimee M, Eyjolfsson, Gudmundur I, Davidsson, Olafur B, Asselbergs, Folkert W, Hreidarsson, Astradur B, Rafnar, Thorunn, Thorleifsson, Gudmar, Edvardsson, Vidar, Sigurdsson, Gunnar, Helgadottir, Anna, Halldorsson, Bjarni V, Masson, Gisli, Holm, Hilma, Onundarson, Pall T, Indridason, Olafur S, Benediktsson, Rafn, Palsson, Runolfur, Gudbjartsson, Daniel F, Olafsson, Isleifur, Thorsteinsdottir, Unnur, Sulem, Patrick, Stefansson, Kari, Onderzoek Precision medicine, Circulatory Health, Team Medisch, Benonisdottir, Stefania, Kristjansson, Ragnar P, Oddsson, Asmundur, Steinthorsdottir, Valgerdur, Mikaelsdottir, Evgenia, Kehr, Birte, Jensson, Brynjar O, Arnadottir, Gudny A, Sulem, Gerald, Sveinbjornsson, Gardar, Kristmundsdottir, Snaedis, Ivarsdottir, Erna V, Vogel, Lotte K, Tragante, Vinicius, Gunnarsson, Bjarni, Runolfsdottir, Hrafnhildur Linnet, Arthur, Joseph G, Deaton, Aimee M, Eyjolfsson, Gudmundur I, Davidsson, Olafur B, Asselbergs, Folkert W, Hreidarsson, Astradur B, Rafnar, Thorunn, Thorleifsson, Gudmar, Edvardsson, Vidar, Sigurdsson, Gunnar, Helgadottir, Anna, Halldorsson, Bjarni V, Masson, Gisli, Holm, Hilma, Onundarson, Pall T, Indridason, Olafur S, Benediktsson, Rafn, Palsson, Runolfur, Gudbjartsson, Daniel F, Olafsson, Isleifur, Thorsteinsdottir, Unnur, Sulem, Patrick, and Stefansson, Kari
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- 2019
11. Sequence variants associating with urinary biomarkers
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Benonisdottir, Stefania, primary, Kristjansson, Ragnar P, additional, Oddsson, Asmundur, additional, Steinthorsdottir, Valgerdur, additional, Mikaelsdottir, Evgenia, additional, Kehr, Birte, additional, Jensson, Brynjar O, additional, Arnadottir, Gudny A, additional, Sulem, Gerald, additional, Sveinbjornsson, Gardar, additional, Kristmundsdottir, Snaedis, additional, Ivarsdottir, Erna V, additional, Tragante, Vinicius, additional, Gunnarsson, Bjarni, additional, Runolfsdottir, Hrafnhildur Linnet, additional, Arthur, Joseph G, additional, Deaton, Aimee M, additional, Eyjolfsson, Gudmundur I, additional, Davidsson, Olafur B, additional, Asselbergs, Folkert W, additional, Hreidarsson, Astradur B, additional, Rafnar, Thorunn, additional, Thorleifsson, Gudmar, additional, Edvardsson, Vidar, additional, Sigurdsson, Gunnar, additional, Helgadottir, Anna, additional, Halldorsson, Bjarni V, additional, Masson, Gisli, additional, Holm, Hilma, additional, Onundarson, Pall T, additional, Indridason, Olafur S, additional, Benediktsson, Rafn, additional, Palsson, Runolfur, additional, Gudbjartsson, Daniel F, additional, Olafsson, Isleifur, additional, Thorsteinsdottir, Unnur, additional, Sulem, Patrick, additional, and Stefansson, Kari, additional
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- 2018
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12. Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA
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Gudmundsson, Julius, primary, Sigurdsson, Jon K., additional, Stefansdottir, Lilja, additional, Agnarsson, Bjarni A., additional, Isaksson, Helgi J., additional, Stefansson, Olafur A., additional, Gudjonsson, Sigurjon A., additional, Gudbjartsson, Daniel F., additional, Masson, Gisli, additional, Frigge, Michael L., additional, Stacey, Simon N., additional, Sulem, Patrick, additional, Halldorsson, Gisli H., additional, Tragante, Vinicius, additional, Holm, Hilma, additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Olafsson, Isleifur, additional, Jonsson, Thorvaldur, additional, Jonsson, Eirikur, additional, Barkardottir, Rosa B., additional, Hilmarsson, Rafn, additional, Asselbergs, Folkert W., additional, Geirsson, Gudmundur, additional, Thorsteinsdottir, Unnur, additional, Rafnar, Thorunn, additional, Thorleifsson, Gudmar, additional, and Stefansson, Kari, additional
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- 2018
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13. Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease
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Helgadottir, Anna, primary, Sulem, Patrick, additional, Thorgeirsson, Gudmundur, additional, Gretarsdottir, Solveig, additional, Thorleifsson, Gudmar, additional, Jensson, Brynjar Ö, additional, Arnadottir, Gudny A, additional, Olafsson, Isleifur, additional, Eyjolfsson, Gudmundur I, additional, Sigurdardottir, Olof, additional, Thorsteinsdottir, Unnur, additional, Gudbjartsson, Daniel F, additional, Holm, Hilma, additional, and Stefansson, Kari, additional
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- 2018
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14. Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA
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Gudmundsson, Julius, Sigurdsson, Jon K, Stefansdottir, Lilja, Agnarsson, Bjarni A, Isaksson, Helgi J, Stefansson, Olafur A, Gudjonsson, Sigurjon A, Gudbjartsson, Daniel F, Masson, Gisli, Frigge, Michael L, Stacey, Simon N, Sulem, Patrick, Halldorsson, Gisli H, Tragante, Vinicius, Holm, Hilma, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Jonsson, Thorvaldur, Jonsson, Eirikur, Barkardottir, Rosa B, Hilmarsson, Rafn, Geirsson, Gudmundur, Asselbergs, Folkert W, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Thorleifsson, Gudmar, Stefansson, Kari, Gudmundsson, Julius, Sigurdsson, Jon K, Stefansdottir, Lilja, Agnarsson, Bjarni A, Isaksson, Helgi J, Stefansson, Olafur A, Gudjonsson, Sigurjon A, Gudbjartsson, Daniel F, Masson, Gisli, Frigge, Michael L, Stacey, Simon N, Sulem, Patrick, Halldorsson, Gisli H, Tragante, Vinicius, Holm, Hilma, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Jonsson, Thorvaldur, Jonsson, Eirikur, Barkardottir, Rosa B, Hilmarsson, Rafn, Geirsson, Gudmundur, Asselbergs, Folkert W, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Thorleifsson, Gudmar, and Stefansson, Kari
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- 2018
15. Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA
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Onderzoek Precision medicine, Circulatory Health, Team Medisch, Gudmundsson, Julius, Sigurdsson, Jon K, Stefansdottir, Lilja, Agnarsson, Bjarni A, Isaksson, Helgi J, Stefansson, Olafur A, Gudjonsson, Sigurjon A, Gudbjartsson, Daniel F, Masson, Gisli, Frigge, Michael L, Stacey, Simon N, Sulem, Patrick, Halldorsson, Gisli H, Tragante, Vinicius, Holm, Hilma, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Jonsson, Thorvaldur, Jonsson, Eirikur, Barkardottir, Rosa B, Hilmarsson, Rafn, Geirsson, Gudmundur, Asselbergs, Folkert W, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Thorleifsson, Gudmar, Stefansson, Kari, Onderzoek Precision medicine, Circulatory Health, Team Medisch, Gudmundsson, Julius, Sigurdsson, Jon K, Stefansdottir, Lilja, Agnarsson, Bjarni A, Isaksson, Helgi J, Stefansson, Olafur A, Gudjonsson, Sigurjon A, Gudbjartsson, Daniel F, Masson, Gisli, Frigge, Michael L, Stacey, Simon N, Sulem, Patrick, Halldorsson, Gisli H, Tragante, Vinicius, Holm, Hilma, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Jonsson, Thorvaldur, Jonsson, Eirikur, Barkardottir, Rosa B, Hilmarsson, Rafn, Geirsson, Gudmundur, Asselbergs, Folkert W, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Thorleifsson, Gudmar, and Stefansson, Kari
- Published
- 2018
16. Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci
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Paul, Ds, Albers, Ca, Rendon, A, Voss, K, Stephens, J, Akkerman, Jan Willem N., Albers, Cornelis A., Ale, Algra, Abtehale Al Hussani, Hooman, Allayee, Franco, Anni, Asselbergs, Folkert W., Antony, Attwood, Beverley, Balkau, Stefania, Bandinelli, François, Bastardot, Saonli, Basu, Baumeister, Sebastian E., Jacques, Beckmann, Beben, Benyamin, Ginevra, Biino, Bis, Joshua C., Lorenzo, Bomba, Amélie, Bonnefond, Boomsma, Dorret I., Bradley, John R., François, Cambien, Chambers, John C., Marina, Ciullo, Cookson, William O., Francesco, Cucca, Ana, Cvejic, D'Adamo, ADAMO PIO, John, Danesh, Fabrice, Danjou, Debashish, Das, Gail, Davies, Paul IW de Bakker, de Boer, Rudolf A., Eco JC de Geus, Deary, Ian J., Dedoussis, George V., Panos, Deloukas, Maria, Dimitriou, Christian, Dina, Angela, Döring, Ulrich, Elling, David, Ellinghaus, Paul, Elliott, Gunnar, Engström, Jeanette, Erdmann, Tõnu, Esko, Evans, David M., Eyjolfsson, Gudmundur I., Mario, Falchi, Wei, Feng, Ferreira, Manuel A., Luigi, Ferrucci, Krista, Fischer, Folsom, Aaron R., Paolo, Fortina, Andre, Franke, Lude, Franke, Frazer, Ian H., Philippe, Froguel, Renzo, Galanello, Ganesh, Santhi K., Garner, Stephen F., Gasparini, Paolo, Bernd, Genser, Gibson, Quince D., Christian, Gieger, Girotto, Giorgia, Glazer, Nicole L., Martin, Gögele, Goodall, Alison H., Andreas, Greinacher, Gudbjartsson, Daniel F., Chris, Hammond, Harris, Sarah E., Jaana, Hartiala, Anna Liisa Hartikainen, Hazen, Stanley L., Heckbert, Susan R., Hedblad, Bo, Christian, Hengstenberg, Micha, Hersch, Hicks, Andrew A., Hilma, Holm, Jouke Jan Hottenga, Thomas, Illig, Marjo Riitta Jarvelin, Jennifer, Jolley, Steve, Jupe, Mika, Kähönen, Naoyuki, Kamatani, Stavroula, Kanoni, Kema, Ido P., Kemp, John P., Jyoti, Khadake, Kay Tee Khaw, Kleber, Marcus E., Kooner, Jaspal S., Peter, Kovacs, Brigitte, Kühnel, Marie Christine Kyrtsonis, Yann, Labrune, Vasiliki, Lagou, Claudia, Langenberg, Terho, Lehtimäki, Xinzhong, Li, Liming, Liang, Lifelines Cohort Study, Heather Lloyd Jones, Ruth JF Loos, Lopez, Lorna M., Thomas, Lumley, Leo Pekka Lyytikäinen, Winfried, Maerz, Reedik, Mägi, Massimo, Mangino, Martin, Nicholas G., Andrea, Maschio, Irene Mateo Leach, Barbara, Mcknight, Stuart, Meacham, Medland, Sarah E., Christa, Meisinger, Olle, Melander, Yasin, Memari, Andres, Metspalu, Kathy, Miller, Mitchell, Braxton D., Moffatt, Miriam F., Montgomery, Grant W., Carmel, Moore, Federico, Murgia, Yusuke, Nakamura, Matthias, Nauck, Gerjan, Navis, Nolte, Ilja M., Ute, Nöthlings, Teresa, Nutile, Yukinori, Okada, Isleifur, Olafsson, Onundarson, Pall T., O’Reilly, Paul F., Ouwehand, Willem H., Debora, Parracciani, Afshin, Parsa, Paul, Dirk S., Penninger, Josef M., Penninx, Brenda W., Mario, Pirastu, Pirastu, Nicola, Giorgio, Pistis, Eleonora, Porcu, Laura, Portas, David, Porteous, Anneli, Pouta, Pramstaller, Peter P., Inga, Prokopenko, Psaty, Bruce M., Janne, Pullat, Aparna, Radhakrishnan, Olli, Raitakari, Ramiro Ramirez Solis, Augusto, Rendon, Ried, Janina S., Ring, Susan M., Robino, Antonietta, Rotter, Jerome I., Daniela, Ruggiero, Aimo, Ruokonen, Cinzia, Sala, Andres, Saluments, Samani, Nilesh J., Jennifer, Sambrook, Serena, Sanna, David, Schlessinger, Schmidt, Carsten O., Stefan, Schreiber, Heribert, Schunkert, James, Scott, Joban, Sehmi, Jovana Serbanovic Canic, So Youn Shin, Shuldiner, Alan R., Rob, Sladek, Smit, Johannes H., George Davey Smith, Gustav Smith, J., Smith, Nicholas L., Harold, Snieder, Nicole, Soranzo, Rossella, Sorice, Spector, Timothy D., Starr, John M., Kari, Stefansson, Derek, Stemple, Jonathan, Stephens, Michael, Stumvoll, Patrick, Sulem, Atsushi, Takahashi, Sian Tsung Tan, Toshiko, Tanaka, Clara, Tang, Weihong, Tang, WH Wilson Tang, Kent, Taylor, Albert, Tenesa, Alexander, Teumer, Swee Lay Thein, Unnur, Thorsteinsdottir, Daniela, Toniolo, Anke, Tönjes, Traglia, Michela, Manuela, Uda, Sheila, Ulivi, Pim van der Harst, Ellen van der Schoot, C., van Gilst, Wiek H., Joost van Pelt, L., van Veldhuisen, Dirk J., Niek, Verweij, Visscher, Peter M., Uwe, Völker, Peter, Vollenweider, Katrin, Voss, Wareham, Nicholas J., Lorenz, Wernisch, Harm Jan Westra, Whitfield, John B., Herich, Wichmann, Wiggins, Kerri L., Gonneke, Willemsen, Winkelmann, Bernhard R., Gerald, Wirnsberger, Bruce HR Wolffenbuttel, Jian, Yang, Tsun Po Yang, Weihua, Zhang, Jing Hua Zhao, Paavo, Zitting, Jaap Jan Zwaginga, van der Harst, P, Chambers, Jc, Soranzo, N, Ouwehand, Wh, Deloukas, P., Paul, D, Albers, Ca, Rendon, A, Voss, K, Stephens, J, Jan Willem N., Akkerman, Cornelis A., Alber, Ale, Algra, Abtehale Al, Hussani, Hooman, Allayee, Franco, Anni, Folkert W., Asselberg, Antony, Attwood, Beverley, Balkau, Stefania, Bandinelli, François, Bastardot, Saonli, Basu, Sebastian E., Baumeister, Jacques, Beckmann, Beben, Benyamin, Ginevra, Biino, Joshua C., Bi, Lorenzo, Bomba, Amélie, Bonnefond, Dorret I., Boomsma, John R., Bradley, François, Cambien, John C., Chamber, Marina, Ciullo, William O., Cookson, Francesco, Cucca, Ana, Cvejic, D'Adamo, ADAMO PIO, John, Danesh, Fabrice, Danjou, Debashish, Da, Gail, Davie, Paul IW de, Bakker, Rudolf A., de Boer, Eco JC de, Geu, Ian J., Deary, George V., Dedoussi, Panos, Delouka, Maria, Dimitriou, Christian, Dina, Angela, Döring, Ulrich, Elling, David, Ellinghau, Paul, Elliott, Gunnar, Engström, Jeanette, Erdmann, Tõnu, Esko, David M., Evan, Gudmundur I., Eyjolfsson, Mario, Falchi, Wei, Feng, Manuel A., Ferreira, Luigi, Ferrucci, Krista, Fischer, Aaron R., Folsom, Paolo, Fortina, Andre, Franke, Lude, Franke, Ian H., Frazer, Philippe, Froguel, Renzo, Galanello, Santhi K., Ganesh, Stephen F., Garner, Gasparini, Paolo, Bernd, Genser, Quince D., Gibson, Christian, Gieger, Girotto, Giorgia, Nicole L., Glazer, Martin, Gögele, Alison H., Goodall, Andreas, Greinacher, Daniel F., Gudbjartsson, Chris, Hammond, Sarah E., Harri, Jaana, Hartiala, Anna Liisa, Hartikainen, Stanley L., Hazen, Susan R., Heckbert, Bo, Hedblad, Christian, Hengstenberg, Micha, Hersch, Andrew A., Hick, Hilma, Holm, Jouke Jan, Hottenga, Thomas, Illig, Marjo Riitta, Jarvelin, Jennifer, Jolley, Steve, Jupe, Mika, Kähönen, Naoyuki, Kamatani, Stavroula, Kanoni, Ido P., Kema, John P., Kemp, Jyoti, Khadake, Kay Tee, Khaw, Marcus E., Kleber, Jaspal S., Kooner, Peter, Kovac, Brigitte, Kühnel, Marie Christine, Kyrtsoni, Yann, Labrune, Vasiliki, Lagou, Claudia, Langenberg, Terho, Lehtimäki, Xinzhong, Li, Liming, Liang, Lifelines Cohort, Study, Heather Lloyd, Jone, Ruth JF, Loo, Lorna M., Lopez, Thomas, Lumley, Leo Pekka, Lyytikäinen, Winfried, Maerz, Reedik, Mägi, Massimo, Mangino, Nicholas G., Martin, Andrea, Maschio, Irene Mateo, Leach, Barbara, Mcknight, Stuart, Meacham, Sarah E., Medland, Christa, Meisinger, Olle, Melander, Yasin, Memari, Andres, Metspalu, Kathy, Miller, Braxton D., Mitchell, Miriam F., Moffatt, Grant W., Montgomery, Carmel, Moore, Federico, Murgia, Yusuke, Nakamura, Matthias, Nauck, Gerjan, Navi, Ilja M., Nolte, Ute, Nöthling, Teresa, Nutile, Yukinori, Okada, Isleifur, Olafsson, Pall T., Onundarson, Paul F., O’Reilly, Willem H., Ouwehand, Debora, Parracciani, Afshin, Parsa, Dirk S., Paul, Josef M., Penninger, Brenda W., Penninx, Mario, Pirastu, Pirastu, Nicola, Giorgio, Pisti, Eleonora, Porcu, Laura, Porta, David, Porteou, Anneli, Pouta, Peter P., Pramstaller, Inga, Prokopenko, Bruce M., Psaty, Janne, Pullat, Aparna, Radhakrishnan, Olli, Raitakari, Ramiro Ramirez, Soli, Augusto, Rendon, Janina S., Ried, Susan M., Ring, Robino, Antonietta, Jerome I., Rotter, Daniela, Ruggiero, Aimo, Ruokonen, Cinzia, Sala, Andres, Salument, Nilesh J., Samani, Jennifer, Sambrook, Serena, Sanna, David, Schlessinger, Carsten O., Schmidt, Stefan, Schreiber, Heribert, Schunkert, James, Scott, Joban, Sehmi, Jovana Serbanovic, Canic, So Youn, Shin, Alan R., Shuldiner, Rob, Sladek, Johannes H., Smit, George Davey, Smith, J., Gustav Smith, Nicholas L., Smith, Harold, Snieder, Nicole, Soranzo, Rossella, Sorice, Timothy D., Spector, John M., Starr, Kari, Stefansson, Derek, Stemple, Jonathan, Stephen, Michael, Stumvoll, Patrick, Sulem, Atsushi, Takahashi, Sian Tsung, Tan, Toshiko, Tanaka, Clara, Tang, Weihong, Tang, WH Wilson, Tang, Kent, Taylor, Albert, Tenesa, Alexander, Teumer, Swee Lay, Thein, Unnur, Thorsteinsdottir, Daniela, Toniolo, Anke, Tönje, Traglia, Michela, Manuela, Uda, Sheila, Ulivi, Pim van der, Harst, C., Ellen van der Schoot, Wiek H., van Gilst, L., Joost van Pelt, Dirk J., van Veldhuisen, Niek, Verweij, Peter M., Visscher, Uwe, Völker, Peter, Vollenweider, Katrin, Vo, Nicholas J., Wareham, Lorenz, Wernisch, Harm Jan, Westra, John B., Whitfield, Herich, Wichmann, Kerri L., Wiggin, Gonneke, Willemsen, Bernhard R., Winkelmann, Gerald, Wirnsberger, Bruce HR, Wolffenbuttel, Jian, Yang, Tsun Po, Yang, Weihua, Zhang, Jing Hua, Zhao, Paavo, Zitting, Jaap Jan, Zwaginga, van der Harst, P, Chambers, Jc, Soranzo, N, Ouwehand, Wh, Deloukas, P., Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England, UCL, UCL Canc Inst, London WC1E 6BT, England, Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England, Natl Hlth Serv NHS Blood & Transplant, Cambridge CB2 0PT, England, Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands, Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England, NIHR Biomed Res Ctr, Cambridge CB2 0PT, England, Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands, Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 GZ Groningen, Netherlands, Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1NY, England, Hammersmith Hosp, Imperial Coll Healthcare NHS Trust, London W12 0HS, England, Royal Brompton & Harefield Hosp NHS Trust, London SW3 6NP, England, Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England, Psychiatry, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, and Cardiovascular Centre (CVC)
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Netherlands Twin Register (NTR) ,Erythrocytes ,Genome-wide association study ,UNCERTAINTY ,Regulatory Sequences, Nucleic Acid ,VARIANTS ,ANNOTATION ,COLORECTAL-CANCER ,Histones ,0302 clinical medicine ,BINDING ,Cluster Analysis ,Myeloid Cells ,Genetics (clinical) ,Genetics ,hematological trait ,0303 health sciences ,Chromosome Mapping ,MRP4 ABCC4 ,Chromatin ,Nucleosomes ,Phenotype ,Organ Specificity ,030220 oncology & carcinogenesis ,Blood Platelets ,Quantitative Trait Loci ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,DYNAMIN 3 ,03 medical and health sciences ,Quantitative Trait, Heritable ,MEGAKARYOCYTES ,Humans ,Cell Lineage ,ddc:610 ,GENOME-WIDE ASSOCIATION ,Enhancer ,Transcription factor ,Gene ,ChIA-PET ,030304 developmental biology ,Research ,Genetic Variation ,DNA ,Chromatin Assembly and Disassembly ,Genetic architecture ,Gene Expression Regulation ,Genome-Wide Association Study - Abstract
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits. Marie-Curie Initial Training Network NETSIM British Heart Foundation RG/09/12/28096 National Institutes for Health RP-PG-0310-1002 Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/282510
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- 2013
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17. A rare splice donor mutation in the haptoglobin gene associates with blood lipid levels and coronary artery disease
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Bjornsson, Eythor, primary, Helgason, Hannes, additional, Halldorsson, Gisli, additional, Helgadottir, Anna, additional, Gylfason, Arnaldur, additional, Kehr, Birte, additional, Jonasdottir, Adalbjorg, additional, Jonasdottir, Aslaug, additional, Sigurdsson, Asgeir, additional, Oddsson, Asmundur, additional, Thorleifsson, Gudmar, additional, Magnusson, Olafur Th., additional, Gretarsdottir, Solveig, additional, Zink, Florian, additional, Kristjansson, Ragnar P., additional, Asgeirsdottir, Margret, additional, Swinkels, Dorine W., additional, Kiemeney, Lambertus A., additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Masson, Gisli, additional, Olafsson, Isleifur, additional, Thorgeirsson, Gudmundur, additional, Holm, Hilma, additional, Thorsteinsdottir, Unnur, additional, Gudbjartsson, Daniel F., additional, Sulem, Patrick, additional, and Stefansson, Kari, additional
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- 2017
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18. A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma
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Smith, Dirk, primary, Helgason, Hannes, additional, Sulem, Patrick, additional, Bjornsdottir, Unnur Steina, additional, Lim, Ai Ching, additional, Sveinbjornsson, Gardar, additional, Hasegawa, Haruki, additional, Brown, Michael, additional, Ketchem, Randal R., additional, Gavala, Monica, additional, Garrett, Logan, additional, Jonasdottir, Adalbjorg, additional, Jonasdottir, Aslaug, additional, Sigurdsson, Asgeir, additional, Magnusson, Olafur T., additional, Eyjolfsson, Gudmundur I., additional, Olafsson, Isleifur, additional, Onundarson, Pall Torfi, additional, Sigurdardottir, Olof, additional, Gislason, David, additional, Gislason, Thorarinn, additional, Ludviksson, Bjorn Runar, additional, Ludviksdottir, Dora, additional, Boezen, H. Marike, additional, Heinzmann, Andrea, additional, Krueger, Marcus, additional, Porsbjerg, Celeste, additional, Ahluwalia, Tarunveer S., additional, Waage, Johannes, additional, Backer, Vibeke, additional, Deichmann, Klaus A., additional, Koppelman, Gerard H., additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Masson, Gisli, additional, Thorsteinsdottir, Unnur, additional, Gudbjartsson, Daniel F., additional, Johnston, James A., additional, Jonsdottir, Ingileif, additional, and Stefansson, Kari, additional
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- 2017
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19. A genome-wide association study yields five novel thyroid cancer risk loci
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Gudmundsson, Julius, primary, Thorleifsson, Gudmar, additional, Sigurdsson, Jon K., additional, Stefansdottir, Lilja, additional, Jonasson, Jon G., additional, Gudjonsson, Sigurjon A., additional, Gudbjartsson, Daniel F., additional, Masson, Gisli, additional, Johannsdottir, Hrefna, additional, Halldorsson, Gisli H., additional, Stacey, Simon N., additional, Helgason, Hannes, additional, Sulem, Patrick, additional, Senter, Leigha, additional, He, Huiling, additional, Liyanarachchi, Sandya, additional, Ringel, Matthew D., additional, Aguillo, Esperanza, additional, Panadero, Angeles, additional, Prats, Enrique, additional, Garcia-Castaño, Almudena, additional, De Juan, Ana, additional, Rivera, Fernando, additional, Xu, Li, additional, Kiemeney, Lambertus A., additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Olafsson, Isleifur, additional, Kristvinsson, Hoskuldur, additional, Netea-Maier, Romana T., additional, Jonsson, Thorvaldur, additional, Mayordomo, Jose I., additional, Plantinga, Theo S., additional, Hjartarson, Hannes, additional, Hrafnkelsson, Jon, additional, Sturgis, Erich M., additional, Thorsteinsdottir, Unnur, additional, Rafnar, Thorunn, additional, de la Chapelle, Albert, additional, and Stefansson, Kari, additional
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- 2017
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20. Sequence variants associating with urinary biomarkers.
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Benonisdottir, Stefania, Kristjansson, Ragnar P, Oddsson, Asmundur, Steinthorsdottir, Valgerdur, Mikaelsdottir, Evgenia, Kehr, Birte, Jensson, Brynjar O, Arnadottir, Gudny A, Sulem, Gerald, Sveinbjornsson, Gardar, Kristmundsdottir, Snaedis, Ivarsdottir, Erna V, Tragante, Vinicius, Gunnarsson, Bjarni, Runolfsdottir, Hrafnhildur Linnet, Arthur, Joseph G, Deaton, Aimee M, Eyjolfsson, Gudmundur I, Davidsson, Olafur B, and Asselbergs, Folkert W
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- 2019
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21. A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma
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Smith, Dirk, Helgason, Hannes, Sulem, Patrick, Bjornsdottir, Unnur Steina, Lim, Ai Ching, Sveinbjornsson, Gardar, Hasegawa, Haruki, Brown, Michael, Ketchem, Randal R, Gavala, Monica, Garrett, Logan, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Magnusson, Olafur T, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Onundarson, Pall Torfi, Sigurdardottir, Olof, Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn Runar, Ludviksdottir, Dora, Boezen, H Marike, Heinzmann, Andrea, Krueger, Marcus, Porsbjerg, Celeste, Ahluwalia, Tarunveer S, Waage, Johannes, Backer, Vibeke, Deichmann, Klaus A, Koppelman, Gerard H, Bønnelykke, Klaus, Bisgaard, Hans, Masson, Gisli, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Johnston, James A, Jonsdottir, Ingileif, Stefansson, Kari, Smith, Dirk, Helgason, Hannes, Sulem, Patrick, Bjornsdottir, Unnur Steina, Lim, Ai Ching, Sveinbjornsson, Gardar, Hasegawa, Haruki, Brown, Michael, Ketchem, Randal R, Gavala, Monica, Garrett, Logan, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Magnusson, Olafur T, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Onundarson, Pall Torfi, Sigurdardottir, Olof, Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn Runar, Ludviksdottir, Dora, Boezen, H Marike, Heinzmann, Andrea, Krueger, Marcus, Porsbjerg, Celeste, Ahluwalia, Tarunveer S, Waage, Johannes, Backer, Vibeke, Deichmann, Klaus A, Koppelman, Gerard H, Bønnelykke, Klaus, Bisgaard, Hans, Masson, Gisli, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Johnston, James A, Jonsdottir, Ingileif, and Stefansson, Kari
- Abstract
IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.
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- 2017
22. Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease
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Nioi, Paul, Sigurdsson, Asgeir, Thorleifsson, Gudmar, Helgason, Hannes, Agustsdottir, Arna B, Norddahl, Gudmundur L, Helgadottir, Anna, Magnusdottir, Audur, Jonasdottir, Aslaug, Gretarsdottir, Solveig, Jonsdottir, Ingileif, Steinthorsdottir, Valgerdur, Rafnar, Thorunn, Swinkels, Dorine W, Galesloot, Tessel E, Grarup, Niels, Jørgensen, Torben, Vestergaard, Henrik, Hansen, Torben, Lauritzen, Torsten, Linneberg, Allan, Friedrich, Nele, Krarup, Nikolaj T, Fenger, Mogens, Abildgaard, Ulrik, Hansen, Peter R, Galløe, Anders M, Braund, Peter S, Nelson, Christopher P, Hall, Alistair S, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Patel, Riyaz S, Levey, Allan I, Hayek, Salim, Shah, Svati H, Reilly, Muredach, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Kiemeney, Lambertus A, Quyyumi, Arshed A, Rader, Daniel J, Kraus, William E, Samani, Nilesh J, Pedersen, Oluf, Thorgeirsson, Gudmundur, Masson, Gisli, Holm, Hilma, Gudbjartsson, Daniel, Sulem, Patrick, Thorsteinsdottir, Unnur, Stefansson, Kari, Nioi, Paul, Sigurdsson, Asgeir, Thorleifsson, Gudmar, Helgason, Hannes, Agustsdottir, Arna B, Norddahl, Gudmundur L, Helgadottir, Anna, Magnusdottir, Audur, Jonasdottir, Aslaug, Gretarsdottir, Solveig, Jonsdottir, Ingileif, Steinthorsdottir, Valgerdur, Rafnar, Thorunn, Swinkels, Dorine W, Galesloot, Tessel E, Grarup, Niels, Jørgensen, Torben, Vestergaard, Henrik, Hansen, Torben, Lauritzen, Torsten, Linneberg, Allan, Friedrich, Nele, Krarup, Nikolaj T, Fenger, Mogens, Abildgaard, Ulrik, Hansen, Peter R, Galløe, Anders M, Braund, Peter S, Nelson, Christopher P, Hall, Alistair S, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Patel, Riyaz S, Levey, Allan I, Hayek, Salim, Shah, Svati H, Reilly, Muredach, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Kiemeney, Lambertus A, Quyyumi, Arshed A, Rader, Daniel J, Kraus, William E, Samani, Nilesh J, Pedersen, Oluf, Thorgeirsson, Gudmundur, Masson, Gisli, Holm, Hilma, Gudbjartsson, Daniel, Sulem, Patrick, Thorsteinsdottir, Unnur, and Stefansson, Kari
- Abstract
Background Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. Methods We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability. Results We found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P=1.0×10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P=4.0×10(-6)). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P=1.8×10(-3)). Conclusions ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health a
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- 2016
23. Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase
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Kristjansson, Ragnar P., primary, Oddsson, Asmundur, additional, Helgason, Hannes, additional, Sveinbjornsson, Gardar, additional, Arnadottir, Gudny A., additional, Jensson, Brynjar O., additional, Jonasdottir, Aslaug, additional, Jonasdottir, Adalbjorg, additional, Bragi Walters, G., additional, Sulem, Gerald, additional, Oskarsdottir, Arna, additional, Benonisdottir, Stefania, additional, Davidsson, Olafur B., additional, Masson, Gisli, additional, Th Magnusson, Olafur, additional, Holm, Hilma, additional, Sigurdardottir, Olof, additional, Jonsdottir, Ingileif, additional, Eyjolfsson, Gudmundur I., additional, Olafsson, Isleifur, additional, Gudbjartsson, Daniel F., additional, Thorsteinsdottir, Unnur, additional, Sulem, Patrick, additional, and Stefansson, Kari, additional
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- 2016
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24. Common and rare variants associated with kidney stones and biochemical traits
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Oddsson, Asmundur, primary, Sulem, Patrick, additional, Helgason, Hannes, additional, Edvardsson, Vidar O., additional, Thorleifsson, Gudmar, additional, Sveinbjörnsson, Gardar, additional, Haraldsdottir, Eik, additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Olafsson, Isleifur, additional, Masson, Gisli, additional, Holm, Hilma, additional, Gudbjartsson, Daniel F., additional, Thorsteinsdottir, Unnur, additional, Indridason, Olafur S., additional, Palsson, Runolfur, additional, and Stefansson, Kari, additional
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- 2015
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25. Identification of low-frequency variants associated with gout and serum uric acid levels
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Sulem, Patrick, Gudbjartsson, Daniel F, Walters, G Bragi, Helgadottir, Hafdis T, Helgason, Agnar, Gudjonsson, Sigurjon A, Zanon, Carlo, Besenbacher, Soren, Bjornsdottir, Gyda, Magnusson, Olafur T, Magnusson, Gisli, Hjartarson, Eirikur, Saemundsdottir, Jona, Gylfason, Arnaldur, Jonasdottir, Adalbjorg, Holm, Hilma, Karason, Ari, Rafnar, Thorunn, Stefansson, Hreinn, Andreassen, Ole A, Pedersen, Jesper H, Pack, Allan I, de Visser, Marieke C H, Kiemeney, Lambertus A, Geirsson, Arni J, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Kong, Augustine, Masson, Gisli, Jonsson, Helgi, Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, Stefansson, Kari, Sulem, Patrick, Gudbjartsson, Daniel F, Walters, G Bragi, Helgadottir, Hafdis T, Helgason, Agnar, Gudjonsson, Sigurjon A, Zanon, Carlo, Besenbacher, Soren, Bjornsdottir, Gyda, Magnusson, Olafur T, Magnusson, Gisli, Hjartarson, Eirikur, Saemundsdottir, Jona, Gylfason, Arnaldur, Jonasdottir, Adalbjorg, Holm, Hilma, Karason, Ari, Rafnar, Thorunn, Stefansson, Hreinn, Andreassen, Ole A, Pedersen, Jesper H, Pack, Allan I, de Visser, Marieke C H, Kiemeney, Lambertus A, Geirsson, Arni J, Eyjolfsson, Gudmundur I, Olafsson, Isleifur, Kong, Augustine, Masson, Gisli, Jonsson, Helgi, Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, and Stefansson, Kari
- Abstract
We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.
- Published
- 2011
26. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- Author
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Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari
- Abstract
Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
- Published
- 2009
- Full Text
- View/download PDF
27. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- Author
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Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari
- Abstract
Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
- Published
- 2009
28. Correction: Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases
- Author
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Gudbjartsson, Daniel F., primary, Holm, Hilma, additional, Indridason, Olafur S., additional, Thorleifsson, Gudmar, additional, Edvardsson, Vidar, additional, Sulem, Patrick, additional, de Vegt, Femmie, additional, d'Ancona, Frank C. H., additional, den Heijer, Martin, additional, Wetzels, Jack F. M., additional, Franzson, Leifur, additional, Rafnar, Thorunn, additional, Kristjansson, Kristleifur, additional, Bjornsdottir, Unnur S., additional, Eyjolfsson, Gudmundur I., additional, Kiemeney, Lambertus A., additional, Kong, Augustine, additional, Palsson, Runolfur, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional
- Published
- 2010
- Full Text
- View/download PDF
29. Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases
- Author
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Gudbjartsson, Daniel F., primary, Holm, Hilma, additional, Indridason, Olafur S., additional, Thorleifsson, Gudmar, additional, Edvardsson, Vidar, additional, Sulem, Patrick, additional, de Vegt, Femmie, additional, d'Ancona, Frank C. H., additional, den Heijer, Martin, additional, Franzson, Leifur, additional, Rafnar, Thorunn, additional, Kristjansson, Kristleifur, additional, Bjornsdottir, Unnur S., additional, Eyjolfsson, Gudmundur I., additional, Kiemeney, Lambertus A., additional, Kong, Augustine, additional, Palsson, Runolfur, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional
- Published
- 2010
- Full Text
- View/download PDF
30. Genome-Wide Meta-Analysis for Serum Calcium Identifies Significantly Associated SNPs near the Calcium-Sensing Receptor (CASR) Gene
- Author
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Kapur, Karen, primary, Johnson, Toby, additional, Beckmann, Noam D., additional, Sehmi, Joban, additional, Tanaka, Toshiko, additional, Kutalik, Zoltán, additional, Styrkarsdottir, Unnur, additional, Zhang, Weihua, additional, Marek, Diana, additional, Gudbjartsson, Daniel F., additional, Milaneschi, Yuri, additional, Holm, Hilma, additional, DiIorio, Angelo, additional, Waterworth, Dawn, additional, Li, Yun, additional, Singleton, Andrew B., additional, Bjornsdottir, Unnur S., additional, Sigurdsson, Gunnar, additional, Hernandez, Dena G., additional, DeSilva, Ranil, additional, Elliott, Paul, additional, Eyjolfsson, Gudmundur I., additional, Guralnik, Jack M., additional, Scott, James, additional, Thorsteinsdottir, Unnur, additional, Bandinelli, Stefania, additional, Chambers, John, additional, Stefansson, Kari, additional, Waeber, Gérard, additional, Ferrucci, Luigi, additional, Kooner, Jaspal S., additional, Mooser, Vincent, additional, Vollenweider, Peter, additional, Beckmann, Jacques S., additional, Bochud, Murielle, additional, and Bergmann, Sven, additional
- Published
- 2010
- Full Text
- View/download PDF
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