Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.
Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.
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DOI：
10.1038/s41386-023-01555-x
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发表时间：
2023-06
影响因子：
7.6
通讯作者：
Soler Artigas, Maria
中科院分区：
文献类型：
--
作者：
Vilar-Ribo, Laura;Cabana-Dominguez, Judit;Martorell, Lourdes;Antoni Ramos-Quiroga, Josep;Sanchez-Roige, Sandra;Palmer, Abraham A.;Vilella, Elisabet;Ribases, Marta;Muntane, Gerard;Soler Artigas, Maria
有证据表明，ADHD与预期寿命缩短有关。ADHD患者的死亡率是普通人群的两倍，这与几个因素有关，如不健康的生活方式行为、社会逆境和心理健康问题，这些问题反过来可能会增加死亡率。由于ADHD和寿命是可遗传的，我们使用ADHD和父母寿命的全基因组关联研究(GWAS)的数据作为个体寿命的替代，来估计它们的遗传相关性，识别与这两种表型共同相关的遗传位点，并评估因果关系。我们证实了注意力缺陷多动障碍与双亲寿命之间存在负遗传相关(Rg = −0.36，P = 1.41e−16)。19个独立的基因座与ADHD和父母的寿命共同相关，大多数增加ADHD风险的等位基因与较短的寿命相关。15个基因座是ADHD的新基因，两个基因座在最初的GWAs中已经存在，其父母的寿命。孟德尔随机化分析指出ADHD倾向对寿命的负面因果影响(P = 1.54e−06；Beta = −0.07)，尽管这些结果并未得到所有敏感性分析的证实，还需要进一步的证据。本研究首次提供了ADHD和寿命之间共同的遗传背景的证据，这可能在报道的ADHD对过早死亡风险的影响中发挥作用。这些结果与之前描述精神障碍寿命缩短的流行病学数据一致，并支持ADHD是一种可能对未来生活结果产生负面影响的重要健康状况。
There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = −0.36, P = 1.41e−16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e−06; Beta = −0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.
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影响因子：
26.1
作者：
Catalá-López F;Hutton B;Page MJ;Driver JA;Ridao M;Alonso-Arroyo A;Valencia A;Macías Saint-Gerons D;Tabarés-Seisdedos R
通讯作者：
Tabarés-Seisdedos R
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
8
作者：
Barbaresi, William J.;Colligan, Robert C.;Katusic, Slavica K.
通讯作者：
Katusic, Slavica K.