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DOI 10.1038/s42003-021-01784-0

Медицинская библиотека · Communications biology · 2021

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Hardcastle Alison J, Liskova Petra, Bykhovskaya Yelena, McComish Bennet J, Davidson Alice E, Inglehearn Chris F, Li Xiaohui, Choquet Hélène, Habeeb Mahmoud, Lucas Sionne E M, Sahebjada Srujana, Pontikos Nikolas, Lopez Karla E Rojas, Khawaja Anthony P, Ali Manir, Dudakova Lubica, Skalicka Pavlina, Van Dooren Bart T H, Geerards Annette J M, Haudum Christoph W, Faro Valeria Lo, Tenen Abi, Simcoe Mark J, Patasova Karina, Yarrand Darioush, Yin Jie, Siddiqui Salina, Rice Aine, Farraj Layal Abi, Chen Yii-Der Ida, Rahi Jugnoo S, Krauss Ronald M, Theusch Elisabeth, Charlesworth Jac C, Szczotka-Flynn Loretta, Toomes Carmel, Meester-Smoor Magda A, Richardson Andrea J, Mitchell Paul A, Taylor Kent D, Melles Ronald B, Aldave Anthony J, Mills Richard A, Cao Ke, Chan Elsie, Daniell Mark D, Wang Jie Jin, Rotter Jerome I, Hewitt Alex W, MacGregor Stuart, Klaver Caroline C W, Ramdas Wishal D, Craig Jamie E, Iyengar Sudha K, O'Brart David, Jorgenson Eric, Baird Paul N, Rabinowitz Yaron S, Burdon Kathryn P, Hammond Chris J, Tuft Stephen J, Hysi Pirro G

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Для цитирования: Hardcastle Alison J, Liskova Petra, Bykhovskaya Yelena, McComish Bennet J, Davidson Alice E, Inglehearn Chris F, Li Xiaohui, Choquet Hélène, Habeeb Mahmoud, Lucas Sionne E M, Sahebjada Srujana, Pontikos Nikolas, Lopez Karla E Rojas, Khawaja Anthony P, Ali Manir, Dudakova Lubica, Skalicka Pavlina, Van Dooren Bart T H, Geerards Annette J M, Haudum Christoph W, Faro Valeria Lo, Tenen Abi, Simcoe Mark J, Patasova Karina, Yarrand Darioush, Yin Jie, Siddiqui Salina, Rice Aine, Farraj Layal Abi, Chen Yii-Der Ida, Rahi Jugnoo S, Krauss Ronald M, Theusch Elisabeth, Charlesworth Jac C, Szczotka-Flynn Loretta, Toomes Carmel, Meester-Smoor Magda A, Richardson Andrea J, Mitchell Paul A, Taylor Kent D, Melles Ronald B, Aldave Anthony J, Mills Richard A, Cao Ke, Chan Elsie, Daniell Mark D, Wang Jie Jin, Rotter Jerome I, Hewitt Alex W, MacGregor Stuart, Klaver Caroline C W, Ramdas Wishal D, Craig Jamie E, Iyengar Sudha K, O'Brart David, Jorgenson Eric, Baird Paul N, Rabinowitz Yaron S, Burdon Kathryn P, Hammond Chris J, Tuft Stephen J, Hysi Pirro G. A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.. Communications biology. 2021. DOI: 10.1038/s42003-021-01784-0.

Предметные рубрики MeSH

HumansAustraliaCase-Control StudiesCell DifferentiationCollagenEuropeExtracellular MatrixGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyKeratoconusPhenotypePolymorphism, Single NucleotideRisk AssessmentRisk Factors
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