Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.
Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data.
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DOI：
10.1111/j.1474-9726.2010.00627.x
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发表时间：
2010-12
期刊：
影响因子：
7.8
通讯作者：
Christiansen L
中科院分区：
文献类型：
--
作者：
Soerensen M;Dato S;Christensen K;McGue M;Stevnsner T;Bohr VA;Christiansen L
FOXO3A 的遗传变异此前已被认为与人类长寿有关。迄今为止发表的研究都是病例对照研究，因此容易受到队列效应带来的偏差的影响。在这项研究中，我们应用纵向研究设计和病例对照研究设计，扩展了先前在最年长丹麦人队列（丹麦1905年队列，N = 1089）和中年丹麦人（N = 736）中的研究结果。选择了 15 个 SNP 以涵盖 FOXO3A 中已知的常见变异。比较最年长的老年人和中年人的 SNP 频率，我们发现了 8 个 SNP 的关联（经过多次测试校正后）； 4（rs13217795、rs2764264、rs479744 和 rs9400239）先前报道与长寿相关，还有四个新的 SNP（rs12206094、rs13220810、rs7762395 和 rs9486902（校正后的 P 值）此外，我们发现 rs9486902、rs10499051 和 rs12206094 的单倍型 TAC 和 CAC（校正后的 P 值：0.01–0.03）与寿命相关。经过多次测试校正（Bonferroni 校正）后，没有 SNP 仍然显着。因此，我们的结果支持并扩展了 FOXO3A 作为从年轻到老年生存的候选长寿基因的作用，但在老年期间则不然。
Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case–control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N = 1089) and middle-aged Danes (N = 736), applying a longitudinal study design as well as the case–control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001–0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01–0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.
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影响因子：
7.8
作者：
Pawlikowska L;Hu D;Huntsman S;Sung A;Chu C;Chen J;Joyner AH;Schork NJ;Hsueh WC;Reiner AP;Psaty BM;Atzmon G;Barzilai N;Cummings SR;Browner WS;Kwok PY;Ziv E;Study of Osteoporotic Fractures
通讯作者：
Study of Osteoporotic Fractures
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作者：
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通讯作者：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0809594106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Flachsbart, Friederike;Caliebeb, Amke;Nebel, Almut
通讯作者：
Nebel, Almut
DOI：
10.1093/gerona/61.4.355
发表时间：
2006-04-01
影响因子：
5.1
作者：
Beekman, M;Blauw, GJ;Slagboom, PE
通讯作者：
Slagboom, PE