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Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-20 , DOI: 10.1038/s41398-019-0613-4 Keira J A Johnston 1, 2, 3 , Mark J Adams 4 , Barbara I Nicholl 1 , Joey Ward 1 , Rona J Strawbridge 1, 5 , Andrew M McIntosh 4 , Daniel J Smith 1 , Mark E S Bailey 3
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-20 , DOI: 10.1038/s41398-019-0613-4 Keira J A Johnston 1, 2, 3 , Mark J Adams 4 , Barbara I Nicholl 1 , Joey Ward 1 , Rona J Strawbridge 1, 5 , Andrew M McIntosh 4 , Daniel J Smith 1 , Mark E S Bailey 3
Affiliation
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Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.
中文翻译：
使用重度抑郁症的条件错误发现率分析来识别与慢性疼痛相关的新型常见变异，并评估 LRFN5 的多效性。
慢性疼痛是一种复杂的特征，具有一定的遗传性，并且在遗传和表型上与重度抑郁症（MDD）相关。使用条件错误发现率 (cFDR) 方法，利用现有 GWAS 输出中识别的多效性，已成功发现相关表型中的新相关变异。在这里，von Korff 慢性疼痛分级和 MDD 的全基因组关联研究输出被用来识别分别满足每个结果表型的 cFDR 阈值的变异，以及满足两种表型的联合 cFDR (ccFDR) 阈值的变异。使用适度保守的阈值，我们总共鉴定了 11 个新的单核苷酸多态性 (SNP)，其中 6 个与慢性疼痛等级相关，其中 9 个与 MDD 相关。 14 号染色体上的四个 SNP 与慢性疼痛分级和 MDD 相关。仅与慢性疼痛分级相关的 SNP 位于 12 号染色体上的 SLC16A7 内。仅与 MDD 相关的 SNP 位于 1 号染色体上包含 LINC01360、LRRIQ3、FPGT 和 FPGT-TNNI3K 的基因密集区域，或者位于 1 号染色体上的 LRFN5 内/附近。 14 号染色体。与这两种结果相关的 SNP 也位于 LRFN5 内。 1 号和 14 号染色体上的几个 SNP 被确定与大脑和中枢神经系统中附近基因的表达水平相关。总体而言，使用 cFDR 方法，我们确定了几个与慢性疼痛相关的新基因位点，并描述了最近确定的 MDD 基因座对慢性疼痛可能的多效性影响。
更新日期：2019-11-20
中文翻译：
使用重度抑郁症的条件错误发现率分析来识别与慢性疼痛相关的新型常见变异，并评估 LRFN5 的多效性。
慢性疼痛是一种复杂的特征，具有一定的遗传性，并且在遗传和表型上与重度抑郁症（MDD）相关。使用条件错误发现率 (cFDR) 方法，利用现有 GWAS 输出中识别的多效性，已成功发现相关表型中的新相关变异。在这里，von Korff 慢性疼痛分级和 MDD 的全基因组关联研究输出被用来识别分别满足每个结果表型的 cFDR 阈值的变异，以及满足两种表型的联合 cFDR (ccFDR) 阈值的变异。使用适度保守的阈值，我们总共鉴定了 11 个新的单核苷酸多态性 (SNP)，其中 6 个与慢性疼痛等级相关，其中 9 个与 MDD 相关。 14 号染色体上的四个 SNP 与慢性疼痛分级和 MDD 相关。仅与慢性疼痛分级相关的 SNP 位于 12 号染色体上的 SLC16A7 内。仅与 MDD 相关的 SNP 位于 1 号染色体上包含 LINC01360、LRRIQ3、FPGT 和 FPGT-TNNI3K 的基因密集区域，或者位于 1 号染色体上的 LRFN5 内/附近。 14 号染色体。与这两种结果相关的 SNP 也位于 LRFN5 内。 1 号和 14 号染色体上的几个 SNP 被确定与大脑和中枢神经系统中附近基因的表达水平相关。总体而言，使用 cFDR 方法，我们确定了几个与慢性疼痛相关的新基因位点，并描述了最近确定的 MDD 基因座对慢性疼痛可能的多效性影响。
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