Multi-omics characterization of type 2 diabetes associated genetic variation. DOI
Ravi Mandla, Kimberly Lorenz, Xianyong Yin

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 15, 2024

Abstract Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information 16 multi-tissue and multi-ancestry expression, protein, metabolite quantitative trait loci (QTL) 46 GWAS for T2D-related traits with largest, most ancestrally diverse T2D to date. Of 1,289 index variants, 716 (56%) demonstrated strong evidence of colocalization molecular or trait, implicating 657 cis -effector genes, 1,691 distal-effector 731 metabolites, 43 traits. We identified 773 these cis- genes using either expression QTL data understudied ancestry groups inclusion variants enriched in underrepresented populations, emphasizing value increasing population diversity functional mapping. Linking into network, elucidated through which T2D-associated variation may impact disease risk. Finally, showed that drugs targeting effector proteins were those approved treat T2D, highlighting potential results prioritize drug targets T2D. These represent leap characterization genetic will aid translating findings novel therapeutic strategies.

Язык: Английский

Multi-omics characterization of type 2 diabetes associated genetic variation. DOI
Ravi Mandla, Kimberly Lorenz, Xianyong Yin

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 15, 2024

Abstract Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information 16 multi-tissue and multi-ancestry expression, protein, metabolite quantitative trait loci (QTL) 46 GWAS for T2D-related traits with largest, most ancestrally diverse T2D to date. Of 1,289 index variants, 716 (56%) demonstrated strong evidence of colocalization molecular or trait, implicating 657 cis -effector genes, 1,691 distal-effector 731 metabolites, 43 traits. We identified 773 these cis- genes using either expression QTL data understudied ancestry groups inclusion variants enriched in underrepresented populations, emphasizing value increasing population diversity functional mapping. Linking into network, elucidated through which T2D-associated variation may impact disease risk. Finally, showed that drugs targeting effector proteins were those approved treat T2D, highlighting potential results prioritize drug targets T2D. These represent leap characterization genetic will aid translating findings novel therapeutic strategies.

Язык: Английский

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