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The Polygenic and Monogenic Basis of Blood Traits and Diseases.

ABSTRACT: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.

SUBMITTER: Vuckovic D 

PROVIDER: S-EPMC7482360 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Vuckovic Dragana D   Bao Erik L EL   Akbari Parsa P   Lareau Caleb A CA   Mousas Abdou A   Jiang Tao T   Chen Ming-Huei MH   Raffield Laura M LM   Tardaguila Manuel M   Huffman Jennifer E JE   Ritchie Scott C SC   Megy Karyn K   Ponstingl Hannes H   Penkett Christopher J CJ   Albers Patrick K PK   Wigdor Emilie M EM   Sakaue Saori S   Moscati Arden A   Manansala Regina R   Lo Ken Sin KS   Qian Huijun H   Akiyama Masato M   Bartz Traci M TM   Ben-Shlomo Yoav Y   Beswick Andrew A   Bork-Jensen Jette J   Bottinger Erwin P EP   Brody Jennifer A JA   van Rooij Frank J A FJA   Chitrala Kumaraswamy N KN   Wilson Peter W F PWF   Choquet Hélène H   Danesh John J   Di Angelantonio Emanuele E   Dimou Niki N   Ding Jingzhong J   Elliott Paul P   Esko Tõnu T   Evans Michele K MK   Felix Stephan B SB   Floyd James S JS   Broer Linda L   Grarup Niels N   Guo Michael H MH   Guo Qi Q   Greinacher Andreas A   Haessler Jeff J   Hansen Torben T   Howson Joanna M M JMM   Huang Wei W   Jorgenson Eric E   Kacprowski Tim T   Kähönen Mika M   Kamatani Yoichiro Y   Kanai Masahiro M   Karthikeyan Savita S   Koskeridis Fotios F   Lange Leslie A LA   Lehtimäki Terho T   Linneberg Allan A   Liu Yongmei Y   Lyytikäinen Leo-Pekka LP   Manichaikul Ani A   Matsuda Koichi K   Mohlke Karen L KL   Mononen Nina N   Murakami Yoshinori Y   Nadkarni Girish N GN   Nikus Kjell K   Pankratz Nathan N   Pedersen Oluf O   Preuss Michael M   Psaty Bruce M BM   Raitakari Olli T OT   Rich Stephen S SS   Rodriguez Benjamin A T BAT   Rosen Jonathan D JD   Rotter Jerome I JI   Schubert Petra P   Spracklen Cassandra N CN   Surendran Praveen P   Tang Hua H   Tardif Jean-Claude JC   Ghanbari Mohsen M   Völker Uwe U   Völzke Henry H   Watkins Nicholas A NA   Weiss Stefan S   Cai Na N   Kundu Kousik K   Watt Stephen B SB   Walter Klaudia K   Zonderman Alan B AB   Cho Kelly K   Li Yun Y   Loos Ruth J F RJF   Knight Julian C JC   Georges Michel M   Stegle Oliver O   Evangelou Evangelos E   Okada Yukinori Y   Roberts David J DJ   Inouye Michael M   Johnson Andrew D AD   Auer Paul L PL   Astle William J WJ   Reiner Alexander P AP   Butterworth Adam S AS   Ouwehand Willem H WH   Lettre Guillaume G   Sankaran Vijay G VG   Soranzo Nicole N  

Cell 20200901 5

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis  ...[more]

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