A proteogenomic signature of age-related macular degeneration in blood

Valur Emilsson, Elias F Gudmundsson, Thorarinn Jonmundsson, Brynjolfur G Jonsson, Michael Twarog, Valborg Gudmundsdottir, Zhiguang Li, Nancy Finkel, Stephen Poor, Xin Liu, Robert Esterberg, Yiyun Zhang, Sandra Jose, Chia-Ling Huang, Sha-Mei Liao, Joseph Loureiro, Qin Zhang, Cynthia L Grosskreutz, Andrew A Nguyen, Qian HuangBarrett Leehy, Rebecca Pitts, Thor Aspelund, John R Lamb, Fridbert Jonasson, Lenore J Launer, Mary Frances Cotch, Lori L Jennings, Vilmundur Gudnason, Tony E Walshe

Rannsóknarafurð: Framlag til fræðitímaritsGreinritrýni

Útdráttur

Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.

Upprunalegt tungumálEnska
Númer greinar3401
Síður (frá-til)3401
FræðitímaritNature Communications
Bindi13
Númer tölublaðs1
DOI
ÚtgáfustaðaÚtgefið - 13 jún. 2022

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© 2022. The Author(s).

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© 2022, The Author(s).

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