2021
DOI: 10.1186/s13195-021-00773-z
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Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits

Abstract: Background Identification of genetic risk factors that are shared between Alzheimer’s disease (AD) and other traits, i.e., pleiotropy, can help improve our understanding of the etiology of AD and potentially detect new therapeutic targets. Previous epidemiological correlations observed between cardiometabolic traits and AD led us to assess the pleiotropy between these traits. Methods We performed a set of bivariate genome-wide association studies c… Show more

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Cited by 22 publications
(12 citation statements)
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References 57 publications
(98 reference statements)
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“…Similarly, a high body-mass index (BMI) increases the risk of AD at midlife, while being protective at older ages (Xu et al, 2011). In line with this hypothesis, genes PTK2B, KANSL1 and ADAM10 have been previously associated with obesity and BMI (Hoffmann et al, 2018;Kichaev et al, 2019;Christakoudi et al, 2021), while ABCA7 and ADAM10 have been associated with blood pressure (Surendran et al, 2020;Bone et al, 2021). In addition, the AD variant in/near IL34 gene codes for a cytokine that is crucial for the differentiation and the maintenance of microglia (Wang and Colonna, 2014): although further studies are needed, an excessive differentiation in middle-age individuals may increase brain-related inflammation and AD-risk, while it might compensate for the slower differentiation and immune activity at very old ages.…”
Section: Different Trajectories Of Effect Of Alzheimer's Disease-associated Variants On Longevitymentioning
confidence: 87%
“…Similarly, a high body-mass index (BMI) increases the risk of AD at midlife, while being protective at older ages (Xu et al, 2011). In line with this hypothesis, genes PTK2B, KANSL1 and ADAM10 have been previously associated with obesity and BMI (Hoffmann et al, 2018;Kichaev et al, 2019;Christakoudi et al, 2021), while ABCA7 and ADAM10 have been associated with blood pressure (Surendran et al, 2020;Bone et al, 2021). In addition, the AD variant in/near IL34 gene codes for a cytokine that is crucial for the differentiation and the maintenance of microglia (Wang and Colonna, 2014): although further studies are needed, an excessive differentiation in middle-age individuals may increase brain-related inflammation and AD-risk, while it might compensate for the slower differentiation and immune activity at very old ages.…”
Section: Different Trajectories Of Effect Of Alzheimer's Disease-associated Variants On Longevitymentioning
confidence: 87%
“…This data set is significantly larger than the GTEx resource (n = 205) that has been used in previous work. 7 Second, we investigate whether SBP mediates the relationship between ACE and AD risk and do not find evidence that supports this. Finally, we explore the associations of genetically proxied cortical ACE expression with other traits and do not find evidence to support that this association applies across other neurodegenerative traits.…”
Section: Discussionmentioning
confidence: 97%
“…Tissue-specific expression has demonstrated that higher cerebellar ACE expression has an association with AD risk. 7 By extension, this implicates a possible detrimental effect of centrally acting pharmacologic ACE inhibition on AD risk. This is of direct clinical relevance because ACE inhibitors are one of the most commonly prescribed antihypertensive agents and are oftentimes commenced as a first-line medication in younger patients.…”
mentioning
confidence: 98%
“…For all NDD but HD, a child term was given, which was also included in the data acquisition step. In total, 153 studies with genomic data were used for the analyses (Maraganore et al, 2005;Fung et al, 2006;Coon et al, 2007;Reiman et al, 2007;Schymick et al, 2007;van Nakamura et al, 2020;Ryu et al, 2020;Alfradique-Dunham et al, 2021;Bone et al, 2021;DeMichele-Sweet et al, 2021;de Rojas et al, 2021;Kang et al, 2021;Loesch et al, 2021;Park et al, 2021;Reddy et al, 2021;Rodrigo and Nyholt, 2021;Sakaue et al, 2021;Schwartzentruber et al, 2021;Shigemizu et al, 2021;Smeland et al, 2021;Tan et al, 2021;Wightman et al, 2021).…”
Section: Data Acquisitionmentioning
confidence: 99%