Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
ABSTRACT We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5×10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5×10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health..
| Medienart: |
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Links: |
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| doi: |
10.1101/2020.09.22.20198937 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
XBI01880649X |
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| 024 | 7 | |a 10.1101/2020.09.22.20198937 |2 doi | |
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| 100 | 1 | |a Mahajan, Anubha |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation |
| 264 | 1 | |c 2024 | |
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| 520 | |a ABSTRACT We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5×10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5×10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health. | ||
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| 700 | 1 | |a Ingelsson, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Zonderman, Alan B |e verfasserin |4 aut | |
| 700 | 1 | |a Psaty, Bruce M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ya-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Rotimi, Charles N |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Diane M |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuda, Fumihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Zeggini, Eleftheria |e verfasserin |0 (orcid)0000-0003-4238-659X |4 aut | |
| 700 | 1 | |a Yokota, Mitsuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Rich, Stephen S |e verfasserin |4 aut | |
| 700 | 1 | |a Kooperberg, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Pankow, James S |e verfasserin |4 aut | |
| 700 | 1 | |a Engert, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yii-Der Ida |e verfasserin |4 aut | |
| 700 | 1 | |a Froguel, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, James G |e verfasserin |4 aut | |
| 700 | 1 | |a Sheu, Wayne HH |e verfasserin |4 aut | |
| 700 | 1 | |a Kardia, Sharon LR |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jer-Yuarn |e verfasserin |4 aut | |
| 700 | 1 | |a Hayes, M Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ronald CW |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Tien-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Groop, Leif |e verfasserin |4 aut | |
| 700 | 1 | |a Mook-Kanamori, Dennis O |e verfasserin |4 aut | |
| 700 | 1 | |a Chandak, Giriraj R |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, Francis S |e verfasserin |4 aut | |
| 700 | 1 | |a Bharadwaj, Dwaipayan |e verfasserin |0 (orcid)0000-0001-5268-8482 |4 aut | |
| 700 | 1 | |a Paré, Guillaume |e verfasserin |0 (orcid)0000-0002-6795-4760 |4 aut | |
| 700 | 1 | |a Sale, Michèle M |e verfasserin |4 aut | |
| 700 | 1 | |a Ahsan, Habibul |e verfasserin |4 aut | |
| 700 | 1 | |a Motala, Ayesha A |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Xiao-Ou |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Kyong-Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Jukema, J Wouter |e verfasserin |4 aut | |
| 700 | 1 | |a Cruz, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a McKean-Cowdin, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Grallert, Harald |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ching-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Bottinger, Erwin P |e verfasserin |4 aut | |
| 700 | 1 | |a Dehghan, Abbas |e verfasserin |4 aut | |
| 700 | 1 | |a Tai, E-Shyong |e verfasserin |4 aut | |
| 700 | 1 | |a Dupuis, Josee |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Norihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Laakso, Markku |e verfasserin |4 aut | |
| 700 | 1 | |a Köttgen, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Koh, Woon-Puay |e verfasserin |4 aut | |
| 700 | 1 | |a Palmer, Colin NA |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Simin |e verfasserin |0 (orcid)0000-0003-2098-3844 |4 aut | |
| 700 | 1 | |a Abecasis, Goncalo |e verfasserin |4 aut | |
| 700 | 1 | |a Kooner, Jaspal S |e verfasserin |4 aut | |
| 700 | 1 | |a Loos, Ruth JF |e verfasserin |4 aut | |
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| 700 | 1 | |a Haiman, Christopher A |e verfasserin |4 aut | |
| 700 | 1 | |a Florez, Jose C |e verfasserin |4 aut | |
| 700 | 1 | |a Saleheen, Danish |e verfasserin |4 aut | |
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| 700 | 1 | |a Maeda, Shiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kadowaki, Takashi |e verfasserin |4 aut | |
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| 700 | 1 | |a Stefansson, Kari |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.09.22.20198937 |x 0 |z kostenfrei |3 Volltext |
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