Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations
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Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations. / Chen, Ming-Huei; Raffield, Laura M.; Mousas, Abdou; Sakaue, Saori; Huffman, Jennifer E.; Moscati, Arden; Trivedi, Bhavi; Jiang, Tao; Akbari, Parsa; Vuckovic, Dragana; Bao, Erik L.; Zhong, Xue; Manansala, Regina; Laplante, Veronique; Chen, Minhui; Lo, Ken Sin; Qian, Huijun; Lareau, Caleb A.; Beaudoin, Melissa; Hunt, Karen A.; Akiyama, Masato; Bartz, Traci M.; Ben-Shlomo, Yoav; Beswick, Andrew; Bork-Jensen, Jette; Bottinger, Erwin P.; Brody, Jennifer A.; van Rooij, Frank J. A.; Chitrala, Kumaraswamynaidu; Cho, Kelly; Choquet, Helene; Correa, Adolfo; Danesh, John; Di Angelantonio, Emanuele; Dimou, Niki; Ding, Jingzhong; Elliott, Paul; Esko, Tonu; Evans, Michele K.; Floyd, James S.; Broer, Linda; Grarup, Niels; Guo, Michael H.; Greinacher, Andreas; Haessler, Jeff; Hansen, Torben; Howson, Joanna M. M.; Linneberg, Allan; Pedersen, Oluf; Loos, Ruth J. F.; VA Million Veteran Program.
I: Cell, Bind 182, Nr. 5, 2020, s. 1198-+.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations
AU - Chen, Ming-Huei
AU - Raffield, Laura M.
AU - Mousas, Abdou
AU - Sakaue, Saori
AU - Huffman, Jennifer E.
AU - Moscati, Arden
AU - Trivedi, Bhavi
AU - Jiang, Tao
AU - Akbari, Parsa
AU - Vuckovic, Dragana
AU - Bao, Erik L.
AU - Zhong, Xue
AU - Manansala, Regina
AU - Laplante, Veronique
AU - Chen, Minhui
AU - Lo, Ken Sin
AU - Qian, Huijun
AU - Lareau, Caleb A.
AU - Beaudoin, Melissa
AU - Hunt, Karen A.
AU - Akiyama, Masato
AU - Bartz, Traci M.
AU - Ben-Shlomo, Yoav
AU - Beswick, Andrew
AU - Bork-Jensen, Jette
AU - Bottinger, Erwin P.
AU - Brody, Jennifer A.
AU - van Rooij, Frank J. A.
AU - Chitrala, Kumaraswamynaidu
AU - Cho, Kelly
AU - Choquet, Helene
AU - Correa, Adolfo
AU - Danesh, John
AU - Di Angelantonio, Emanuele
AU - Dimou, Niki
AU - Ding, Jingzhong
AU - Elliott, Paul
AU - Esko, Tonu
AU - Evans, Michele K.
AU - Floyd, James S.
AU - Broer, Linda
AU - Grarup, Niels
AU - Guo, Michael H.
AU - Greinacher, Andreas
AU - Haessler, Jeff
AU - Hansen, Torben
AU - Howson, Joanna M. M.
AU - Linneberg, Allan
AU - Pedersen, Oluf
AU - Loos, Ruth J. F.
AU - VA Million Veteran Program
PY - 2020
Y1 - 2020
N2 - Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p <5310(-9), including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EURmeta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
AB - Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p <5310(-9), including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EURmeta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
KW - GENOME-WIDE ASSOCIATION
KW - FREQUENCY CODING VARIANTS
KW - POLYGENIC RISK SCORES
KW - HUMAN HEMATOPOIESIS
KW - AFRICAN-AMERICANS
KW - SINGLE-CELL
KW - BIOBANK
KW - LOCI
KW - DISEASE
KW - TRAIT
U2 - 10.1016/j.cell.2020.06.045
DO - 10.1016/j.cell.2020.06.045
M3 - Journal article
C2 - 32888493
VL - 182
SP - 1198-+
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -
ID: 250075688