Rare variant analyses across multiethnic cohorts identify novel genes for refractive error.
Rare variant analyses across multiethnic cohorts identify novel genes for refractive error.
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DOI：
10.1038/s42003-022-04323-7
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发表时间：
2023-01-03
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
屈光不正，这里测量为平均等效球镜（SER），是由遗传和环境因素引起的复杂眼部疾病。SER为强正值或负值的个体需要眼镜或其他方法进行视力矫正。全基因组关联研究（GWAS）已经确定了常见的遗传危险因素，但仍有很大一部分屈光不正的遗传力缺失。这种遗传性中的一些可能是由罕见的变异（次要等位基因频率[MAF] ≤ 0.01）解释的。我们对来自屈光不正和近视联合会（CREAM）的外显子组阵列数据中的罕见变异进行了平均球镜当量的多个基于基因的关联检验。该数据集包括来自5个印欧和东亚种族队列的27，000多名受试者。我们确定了129个与屈光不正相关的独特基因，其中许多基因在多个队列中重复。我们最好的新候选者包括视网膜表达的PDCD6IP、昼夜节律基因PER3和影响眼睛形态的P4HTM。未来的工作将包括功能研究和验证。识别导致屈光不正的基因并进一步了解其功能可能会导致更好地治疗和预防屈光不正，屈光不正本身就是各种致盲条件的重要风险因素。对来自27，000多名参与者的外显子组阵列数据进行的多种族荟萃分析确定了几种可能导致眼部屈光不正风险的罕见变异。
Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions. A multi-ethnic meta-analysis of exome array data from over 27,000 participants identifies several rare variants that could contribute to risk of ocular refractive error.
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影响因子：
4.6
作者：
Kawashima-Kumagai K;Yamashiro K;Yoshikawa M;Miyake M;Ming GCC;Fan Q;Koh JY;Saito M;Sugahara-Kuroda M;Oishi M;Akagi-Kurashige Y;Nakata I;Nakanishi H;Gotoh N;Oishi A;Tamura H;Ooto S;Tsujikawa A;Kurimoto Y;Sekiryu T;Matsuda F;Khor CC;Cheng CY;Wong TY;Yoshimura N
通讯作者：
Yoshimura N
影响因子：
4.4
作者：
Cheng, Lijia;Bu, Hong;Lin, Feng
通讯作者：
Lin, Feng
影响因子：
4.4
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Li YJ;Guggenheim JA;Bulusu A;Metlapally R;Abbott D;Malecaze F;Calvas P;Rosenberg T;Paget S;Creer RC;Kirov G;Owen MJ;Zhao B;White T;Mackey DA;Young TL
通讯作者：
Young TL
影响因子：
64.5
作者：
Cowan CS;Renner M;De Gennaro M;Gross-Scherf B;Goldblum D;Hou Y;Munz M;Rodrigues TM;Krol J;Szikra T;Cuttat R;Waldt A;Papasaikas P;Diggelmann R;Patino-Alvarez CP;Galliker P;Spirig SE;Pavlinic D;Gerber-Hollbach N;Schuierer S;Srdanovic A;Balogh M;Panero R;Kusnyerik A;Szabo A;Stadler MB;Orgül S;Picelli S;Hasler PW;Hierlemann A;Scholl HPN;Roma G;Nigsch F;Roska B
通讯作者：
Roska B
影响因子：
5.8
作者：
Bauer-Mehren, Anna;Rautschka, Michael;Furlong, Laura I.
通讯作者：
Furlong, Laura I.