Antonsdottir Inga Margret, Creese Byron, Klei Lambertus, DeMichele-Sweet Mary Ann A, Weamer Elise A, Garcia-Gonzalez Pablo, Marquie Marta, Boada Mercè, Alarcón-Martín Emilio, Valero Sergi, Liu Yushi, Hooli Basavaraj, Aarsland Dag, Selbaek Geir, Bergh Sverre, Rongve Arvid, Saltvedt Ingvild, Skjellegrind Håvard K, Engdahl Bo, Andreassen Ole A, Borroni Barbara, Mecocci Patrizia, Wedatilake Yehani, Mayeux Richard, Foroud Tatiana, Ruiz Agustín, Lopez Oscar L, Kamboh M Ilyas, Ballard Clive, Devlin Bernie, Lyketsos Constantine, Sweet Robert A
Johns Hopkins School of Nursing Baltimore Maryland USA.
Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Department of Psychiatry and Behavioral Sciences Johns Hopkins Bayview Johns Hopkins Medicine Baltimore Maryland USA.
Alzheimers Dement (N Y). 2024 May 23;10(2):e12472. doi: 10.1002/trc2.12472. eCollection 2024 Apr-Jun.
Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.
Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P).
AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.
AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.
It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.
阿尔茨海默病（AD）患者通常会出现精神病性神经精神症状（AD+P）和/或情感障碍（抑郁、焦虑和/或易怒，AD+A）。本研究的目的是确定AD+P和AD+A的遗传结构，以及它们的遗传相关表型。
对来自六项源研究的9988名AD参与者进行全基因组关联荟萃分析，这些参与者具有AD+P、AD+A和联合表型（AD+A+P）特征。
AD+P和AD+A在遗传上相关。然而，AD+P和AD+A与无AD个体的精神科表型的遗传相关性有所不同。AD+P与双相情感障碍呈负遗传相关，与抑郁症状呈正相关。AD+A与焦虑症呈正相关，且与抑郁症状的相关性比AD+P更强。AD+P和AD+A+P具有显著的估计遗传力，而AD+A则没有。对与这三种表型关联最强的基因座进行检查，发现了重叠和独特的关联。
AD+P、AD+A和AD+A+P具有共同和不同的遗传关联，这表明将遗传见解纳入未来治疗开发的重要性。
长期以来，人们一直知道精神病性症状和情感症状在被诊断为阿尔茨海默病的个体中常常并存。在这里，我们首次研究了这一临床观察结果背后的遗传结构，确定了阿尔茨海默病中的精神病性和情感表型在遗传上是相关的。然而，阿尔茨海默病中的精神病性和情感表型与在无阿尔茨海默病个体中评估的精神科表型的遗传相关性有所不同。阿尔茨海默病中的精神病与双相情感障碍呈负遗传相关，与抑郁症状呈正相关，而阿尔茨海默病中的情感表型与焦虑症呈正相关，且与抑郁症状的相关性比精神病更强。阿尔茨海默病中的精神病以及联合的精神病性和情感表型具有显著的估计遗传力，而AD中的情感表型则没有。对与精神病性、情感性或联合表型关联最强的基因座进行检查，发现了重叠和独特的关联。
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