Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.
Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.
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DOI：
10.1016/j.ajhg.2014.12.004
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发表时间：
2015-01-08
影响因子：
9.8
通讯作者：
Brown SJ
中科院分区：
文献类型：
--
作者：
Baurecht H;Hotze M;Brand S;Büning C;Cormican P;Corvin A;Ellinghaus D;Ellinghaus E;Esparza-Gordillo J;Fölster-Holst R;Franke A;Gieger C;Hubner N;Illig T;Irvine AD;Kabesch M;Lee YA;Lieb W;Marenholz I;McLean WH;Morris DW;Mrowietz U;Nair R;Nöthen MM;Novak N;O'Regan GM;Psoriasis Association Genetics Extension;Schreiber S;Smith C;Strauch K;Stuart PE;Trembath R;Tsoi LC;Weichenthal M;Barker J;Elder JT;Weidinger S;Cordell HJ;Brown SJ
特应性皮炎和银屑病是影响皮肤的两种最常见的免疫介导的炎症性疾病。全基因组研究显示了高度的遗传重叠，但这些疾病具有相互排斥的临床表型和相反的免疫机制。尽管异位性皮炎和银屑病普遍存在，但它们很少在一个个体内同时发生。通过利用来自> 19，000个个体的全基因组关联研究和免疫芯片数据以及从荟萃分析开发的方法，我们已经在表皮分化复合体内的共享基因座以及独立的疾病特异性基因座上鉴定了相反的风险等位基因。（染色体1q21.3）、Th 2基因座控制区（染色体5q31.1）和主要组织相容性复合体（染色体6p 21 -22）。我们进一步鉴定了PRKRA和ANXA 6/TNIP 1中先前未报道的对特应性皮炎和银屑病风险具有相反作用的多效性等位基因。相比之下，没有证据表明共有的基因座对两种疾病的作用方向相同。我们的研究结果表明，特应性皮炎和银屑病具有不同的遗传机制，在影响表皮分化和免疫反应的共同途径中具有相反的作用。本研究中开发的统计分析方法从先前发表的数据集中产生了额外的见解。该方法可能适用于调查其他复杂性状的遗传基础重叠和独特的临床特征。
Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21–22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.
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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：
30.8
作者：
通讯作者：
--
DOI：
10.1038/jid.2011.24
发表时间：
2011-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Kim BE;Howell MD;Guttman-Yassky E;Gilleaudeau PM;Cardinale IR;Boguniewicz M;Krueger JG;Leung DY
通讯作者：
Leung DY
影响因子：
14.2
作者：
Guttman-Yassky, Emma;Nograles, Kristine E.;Krueger, James G.
通讯作者：
Krueger, James G.
影响因子：
30.8
作者：
Cookson, WOCM;Ubhi, B;Harper, JI
通讯作者：
Harper, JI