Family-Based Genome-Wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus.
Family-Based Genome-Wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus.
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DOI：
10.1167/iovs.17-23536
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发表时间：
2018-05-01
影响因子：
4.4
通讯作者：
Mexican American Glaucoma Genetic Study; International Glaucoma Genetics Consortium; and NEIGHBORHOOD Consortium
中科院分区：
文献类型：
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作者：
Fan BJ;Chen X;Sondhi N;Sharmila PF;Soumittra N;Sripriya S;Sacikala S;Asokan R;Friedman DS;Pasquale LR;Gao XR;Vijaya L;Cooke Bailey J;Vitart V;MacGregor S;Hammond CJ;Khor CC;Haines JL;George R;Wiggs JL;Mexican American Glaucoma Genetic Study; International Glaucoma Genetics Consortium; and NEIGHBORHOOD Consortium
确定导致印度南部个体中央角膜厚度（CCT）的遗传风险因素，该人群具有较高的眼部疾病患病率。使用Omni2.5微珠阵列对来自15个大的南印度家系的195个个体进行基因分型。使用MERLIN中的评分检验进行基于家庭的CCT关联。全基因组关联研究（GWAS）发现WNT7B和CCT的第一个内含子中的单核苷酸多态性（SNP）关联最强（最高SNP rs9330813; β = − 0.57，95%置信区间[CI]：− 0.78至− 0.36; P = 1.7 × 10 − 7）。我们进一步研究了rs9330813在拉丁裔队列和四个独立的欧洲队列。对这些数据集的荟萃分析表明，rs9330813与CCT之间存在统计学显著相关性（β = − 3.94，95%CI：− 5.23至− 2.66; P = 1.7 × 10 − 9）。位于包括rs9330813的相同基因组区域的WNT7B SNP先前与拉丁美洲人的CCT相关，但与日本人群中与近视相关的其他眼部数量性状（角膜曲率和眼轴长度）相关（rs10453441和rs200329677）。为了评估在南印度家族中观察到的WNT7B与CCT相关性的特异性，我们使用在这些相同家族中测量的45个眼部性状（包括角膜曲率和眼轴长度）完成了针对顶级WNT7B SNP的眼部全表型相关性研究（PheWAS）。眼部PheWAS结果表明，在南印度家族中，WNT7B SNP主要与CCT相关。结果表明，在南印度家系中，WNT7B SNP与CCT之间存在关联的有力证据，并表明WNT7B SNP对眼部数量性状具有群体特异性影响。
To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = −0.57, 95% confidence interval [CI]: −0.78 to −0.36; P = 1.7 × 10−7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = −3.94, 95% CI: −5.23 to −2.66; P = 1.7 × 10−9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.
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影响因子：
5.9
作者：
Famili F;Brugman MH;Taskesen E;Naber BEA;Fodde R;Staal FJT
通讯作者：
Staal FJT
影响因子：
46.9
作者：
通讯作者：
--
英国生物库中的遗传分析将胰岛素抵抗和跨内皮迁移途径与冠状动脉疾病联系起来。
影响因子：
30.8
作者：
Klarin D;Zhu QM;Emdin CA;Chaffin M;Horner S;McMillan BJ;Leed A;Weale ME;Spencer CCA;Aguet F;Segrè AV;Ardlie KG;Khera AV;Kaushik VK;Natarajan P;CARDIoGRAMplusC4D Consortium;Kathiresan S
通讯作者：
Kathiresan S
DOI：
10.1146/annurev-genom-090314-024956
发表时间：
2016-08-31
影响因子：
8.7
作者：
Denny JC;Bastarache L;Roden DM
通讯作者：
Roden DM
影响因子：
2
作者：
Kniestedt, C;Lin, S;Stamper, RL
通讯作者：
Stamper, RL