上海精神医学
上海精神醫學
상해정신의학
SHANGHAI ARCHIVES OF PSYCHIATRY
2015年
2期
111-118
,共8页
Zuo LJ%Zhang CK%Sayward FG%Cheung KH%Wang KS%Krystal JH%Zhao HY%Luo XG
Zuo LJ%Zhang CK%Sayward FG%Cheung KH%Wang KS%Krystal JH%Zhao HY%Luo XG
Zuo LJ%Zhang CK%Sayward FG%Cheung KH%Wang KS%Krystal JH%Zhao HY%Luo XG
基于基因的全基因组关联分析%基于通路的全基因组关联分析%细胞-细胞外基质相互作用的通路%PXN%桩蛋白%酒精依赖
基于基因的全基因組關聯分析%基于通路的全基因組關聯分析%細胞-細胞外基質相互作用的通路%PXN%樁蛋白%酒精依賴
기우기인적전기인조관련분석%기우통로적전기인조관련분석%세포-세포외기질상호작용적통로%PXN%장단백%주정의뢰
gene-based GWAS%pathway-based GWAS%cell-extracellular matrix interaction pathway%PXN%paxillin%alcohol dependence
背景：信号通路中风险基因的构成可能可以解释酒精依赖风险基因协同的神经生物学作用。
<br> 目的：识别酒精依赖的风险基因和风险基因通路。
<br> 方法：我们采用基因富集(gene-set-rich)分析方法对酒精依赖进行了基于通路的全基因组关联分析(GWAS)。在包括1409名欧裔美国人(European-American，EA)酒精依赖者和1518名EA健康对照者的探索性样本人群中检测了近一百万个基因标志物。此外，将681名非裔美国人(African-American, AA)病例和508名AA健康受试者作为重测样本。
<br> 结果：我们发现了几个与酒精依赖显著相关的可重复的全基因组风险基因和风险通路。在多重比较Bonferroni校正后，“细胞-细胞外基质相互作用”通路(EA样本中p<2.0E-4)和该通路中PXN基因(编码桩蛋白paxillin)(EA样本中p=3.9E-7)是最有可能的酒精依赖的危险因素。在EA样本(0.015≤p≤0.035)和AA样本(0.025≤p≤0.050)中还有两条富含酒精依赖相关基因的可重复的通路：“Na+/Cl-依赖性神经递质转运体”通路和“其他聚糖降解”通路。
<br> 结论：一些基因和生物信号传导过程可能与酒精依赖的风险相关，本研究的发现为此提供了新的证据。
揹景：信號通路中風險基因的構成可能可以解釋酒精依賴風險基因協同的神經生物學作用。
<br> 目的：識彆酒精依賴的風險基因和風險基因通路。
<br> 方法：我們採用基因富集(gene-set-rich)分析方法對酒精依賴進行瞭基于通路的全基因組關聯分析(GWAS)。在包括1409名歐裔美國人(European-American，EA)酒精依賴者和1518名EA健康對照者的探索性樣本人群中檢測瞭近一百萬箇基因標誌物。此外，將681名非裔美國人(African-American, AA)病例和508名AA健康受試者作為重測樣本。
<br> 結果：我們髮現瞭幾箇與酒精依賴顯著相關的可重複的全基因組風險基因和風險通路。在多重比較Bonferroni校正後，“細胞-細胞外基質相互作用”通路(EA樣本中p<2.0E-4)和該通路中PXN基因(編碼樁蛋白paxillin)(EA樣本中p=3.9E-7)是最有可能的酒精依賴的危險因素。在EA樣本(0.015≤p≤0.035)和AA樣本(0.025≤p≤0.050)中還有兩條富含酒精依賴相關基因的可重複的通路：“Na+/Cl-依賴性神經遞質轉運體”通路和“其他聚糖降解”通路。
<br> 結論：一些基因和生物信號傳導過程可能與酒精依賴的風險相關，本研究的髮現為此提供瞭新的證據。
배경：신호통로중풍험기인적구성가능가이해석주정의뢰풍험기인협동적신경생물학작용。
<br> 목적：식별주정의뢰적풍험기인화풍험기인통로。
<br> 방법：아문채용기인부집(gene-set-rich)분석방법대주정의뢰진행료기우통로적전기인조관련분석(GWAS)。재포괄1409명구예미국인(European-American，EA)주정의뢰자화1518명EA건강대조자적탐색성양본인군중검측료근일백만개기인표지물。차외，장681명비예미국인(African-American, AA)병례화508명AA건강수시자작위중측양본。
<br> 결과：아문발현료궤개여주정의뢰현저상관적가중복적전기인조풍험기인화풍험통로。재다중비교Bonferroni교정후，“세포-세포외기질상호작용”통로(EA양본중p<2.0E-4)화해통로중PXN기인(편마장단백paxillin)(EA양본중p=3.9E-7)시최유가능적주정의뢰적위험인소。재EA양본(0.015≤p≤0.035)화AA양본(0.025≤p≤0.050)중환유량조부함주정의뢰상관기인적가중복적통로：“Na+/Cl-의뢰성신경체질전운체”통로화“기타취당강해”통로。
<br> 결론：일사기인화생물신호전도과정가능여주정의뢰적풍험상관，본연구적발현위차제공료신적증거。
Background:The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence.
<br> Aims:Identify risk genes and risk gene pathways for alcohol dependence.
<br> Methods:We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample.
<br> Results:We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the‘cell-extracellular matrix interactions’ pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050):the‘Na+/Cl-dependent neurotransmitter transporters’ pathway and the‘other glycan degradation’ pathway.
<br> Conclusions:These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence.
