Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus.
Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus.
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DOI：
10.1167/iovs.16-19519
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发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Pericak-Vance MA
中科院分区：
文献类型：
--
作者：
Sardell RJ;Persad PJ;Pan SS;Whitehead P;Adams LD;Laux RA;Fortun JA;Brantley MA Jr;Kovach JL;Schwartz SG;Agarwal A;Haines JL;Scott WK;Pericak-Vance MA
年龄相关性黄斑变性(AMD)的进展速度差异很大，但其与遗传变异的关系尚未得到广泛研究。我们测试了从中度AMD到地理性萎缩(GA)或脉络膜新生血管(CNV)的进展率是否与四个与进展期AMD风险最密切相关的基因的七个单核苷酸多态(SNPs)的基因型相关。COX比例风险生存模型检验了进展时间和SNP基因型之间的关系，同时调整了年龄和性别，并考虑了可变的随访时间、右审查数据和重复测量(左眼和右眼)。CFH：rs10737680，但CFH：rs1061170(Y402H)SNP的进展速度随风险等位基因数目的不同而不同；携带两个风险等位基因的个体比携带一个等位基因的个体进展更快(风险比[HR]=1.61，95%可信区间[CI]=1.08-2.40，P<；0.02，n=547眼)，尽管在Bonferroni校正后这种情况并不显著。这个信号可能是由相关的保护性变异体CFH：rs6677604的关联驱动的，它标记了CFHR1-3的缺失；至少有一个保护性等位基因的个体进展较慢。单独考虑GA和CNV，CFH：rs10737680对CNV进展的作用更强。结果支持先前的发现，AMD进展率受CFH的影响，并提示CFH内的变异可能对风险与进展有不同的影响。然而，由于CFH：rs10737680在Bonferroni校正后并不显著，并且只解释了进展速度中相对较小的一部分变化，超出了年龄的解释，我们认为额外的因素有助于进展。
Progression rate of age-related macular degeneration (AMD) varies substantially, yet its association with genetic variation has not been widely examined. We tested whether progression rate from intermediate AMD to geographic atrophy (GA) or choroidal neovascularization (CNV) was correlated with genotype at seven single nucleotide polymorphisms (SNPs) in the four genes most strongly associated with risk of advanced AMD. Cox proportional hazards survival models examined the association between progression time and SNP genotype while adjusting for age and sex and accounting for variable follow-up time, right censored data, and repeated measures (left and right eyes). Progression rate varied with the number of risk alleles at the CFH:rs10737680 but not the CFH:rs1061170 (Y402H) SNP; individuals with two risk alleles progressed faster than those with one allele (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08–2.40, P < 0.02, n = 547 eyes), although this was not significant after Bonferroni correction. This signal was likely driven by an association at the correlated protective variant, CFH:rs6677604, which tags the CFHR1-3 deletion; individuals with at least one protective allele progressed more slowly. Considering GA and CNV separately showed that the effect of CFH:rs10737680 was stronger for progression to CNV. Results support previous findings that AMD progression rate is influenced by CFH, and suggest that variants within CFH may have different effects on risk versus progression. However, since CFH:rs10737680 was not significant after Bonferroni correction and explained only a relatively small portion of variation in progression rate beyond that explained by age, we suggest that additional factors contribute to progression.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Ansari M;McKeigue PM;Skerka C;Hayward C;Rudan I;Vitart V;Polasek O;Armbrecht AM;Yates JR;Vatavuk Z;Bencic G;Kolcic I;Oostra BA;Van Duijn CM;Campbell S;Stanton CM;Huffman J;Shu X;Khan JC;Shahid H;Harding SP;Bishop PN;Deary IJ;Moore AT;Dhillon B;Rudan P;Zipfel PF;Sim RB;Hastie ND;Campbell H;Wright AF
通讯作者：
Wright AF
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
4.4
作者：
Chew, Emily Y.
通讯作者：
Chew, Emily Y.
DOI：
10.1146/annurev-genom-090413-025610
发表时间：
2014
影响因子：
8.7
作者：
Fritsche LG;Fariss RN;Stambolian D;Abecasis GR;Curcio CA;Swaroop A
通讯作者：
Swaroop A