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Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank
Open accessAbstract
Background The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer's disease (AD) and cardiovascular disease. Due to their clinical significance, we explored disease associations of the APOE genotypes using a hypothesis-free, data-driven, phenome-wide association study (PheWAS) approach. Methods We used data from the UK Biobank to screen for associations between APOE genotypes and over 950 disease outcomes using genotype ε3ε3 as a reference. Data was restricted to 337,484 white British participants (aged 37–73 years). Findings After correction for multiple testing, PheWAS analyses identified associations with 37 outcomes, representing 18 distinct diseases. As expected, ε3ε4 and ε4ε4 genotypes associated with increased odds of AD (p ≤ 7.6 × 10 −46 ), hypercholesterolaemia (p ≤ 7.1 × 10 −17 ) and ischaemic heart disease (p ≤ 2.3 × 10 −4 ), while ε2ε3 provided protection for the latter two conditions (p ≤ 3.7 × 10 −10 ) compared to ε3ε3. In contrast, ε4-associated disease protection was seen against obesity, chronic airway obstruction, type 2 diabetes, gallbladder disease, and liver disease (all p ≤ 5.2 × 10 −4 ) while ε2ε2 homozygosity increased risks of peripheral vascular disease, thromboembolism, arterial aneurysm, peptic ulcer, cervical disorders, and hallux valgus (all p ≤ 6.1 × 10 −4 ). Sensitivity analyses using brain neuroimaging, blood biochemistry, anthropometric, and spirometric biomarkers supported the PheWAS findings on APOE associations with respective disease outcomes. Interpretation PheWAS confirms strong associations between APOE and AD, hypercholesterolaemia, and ischaemic heart disease, and suggests potential ε4-associated disease protection and harmful effects of the ε2ε2 genotype, for several conditions. Funding National Health and Medical Research Council of Australia.
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“By contrast, in the same registries, APOEε2 has been associated with lower LDL cholesterol levels, increased triglyceride levels and increased risk of peripheral vascular disease87,88.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [88]
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“Besides AD43, APOE has been associated with at least eighteen other diseases, including heart disease and high cholesterol44.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [44]
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“APOE genotype was determined using SNP data at rs429358 and rs7412, which define the three major APOE isoforms (ε2, ε3, and ε4) based on established haplotypes. Genotypes were assigned according to allele combinations, consistent with prior UK Biobank studies,79”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [79]
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“a risk increase also recently reported cross-sectionally in the UK Biobank [42]”
From APOE and vascular disease: Sequencing and genotyping in general population cohorts (2023) · cites this paper as [42]
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“In large health registries such as the UK BioBank, the APOEε4 allele has been associated with higher LDL cholesterol and triglycerides levels, lower HDL cholesterol levels and an increased risk of coronary artery disease.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [88]
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Cites
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“1 £ 10 4 to control for multiple testing [10], accounting for all comparisons across the five PheWASs.”
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BackgroundMethodThe UK Biobank resource with deep phenotyping and genomic data
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MethodInfluentialDenny, J. C., Bastarache, L. A., Ritchie, M. D., Carroll, R. J., Zink, R., Mosley, J. D., Field, J. R., Pulley, J. M., Ramirez, A. H., Bowton, E., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2749 · Cited by 987 · cited 1×
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“The homozygous e2e2 genotype increased the odds for a distinct set of disease outcomes not associated with other genotypes, suggesting that these conditions stem from a homozygous loss of APOE function specific to the e2 variant, such as its inability to bind the LDL receptor [22].”
BackgroundR PheWAS: data analysis and plotting tools for phenome-wide association studies in the R environment
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“Chronologically, e4 is believed to be the ancestral allele from which the e3 and e2 variants sequentially evolved over 200,000 years ago [1].”
BackgroundOxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages
Lara-Guzmán, O. J., Gil-Izquierdo, Á., Medina, S., Osorio, E., Álvarez-Quintero, R., Zuluaga, N., Oger, C., Galano, J.-M., Durand, T., & Muñoz-Durango, K. (2018) · Redox Biology · doi:10.1016/j.redox.2017.11.017 · Cited by 194 · cited 7×
“As is typically reported, e2e3 and e2e4 were protective for hypercholesterolaemia compared to e3e3 (with lower levels of “bad” cholesterol indicators; total cholesterol, LDL and APOB). e2e3 also had increased levels of “good” cholesterol indicators (HDL-cholesterol and APOA) and was associated with reduced risk of IHD…”
BackgroundInfluentialTudorache, I. F., Trusca, V. G., & Gafencu, A. V. (2017) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2017.05.003 · Cited by 186 · cited 1×
“The polymorphisms affect the binding affinities of APOE for lipid and the LDLR (appendix p 34 figure S1), resulting in various effects on biomarkers of lipid and cholesterol health, and differential risks of a variety of health outcomes [2].”
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“By contrast, in the same registries, APOE ε2 has been associated with lower LDL cholesterol levels, increased triglyceride levels and increased risk of peripheral vascular disease 87,88 .”
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“Of note, homozygosity for the APOE ε4 allele further increases the risk of developing AD [268].”
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“Furthermore, genetic variations in genes that play a role in lipid metabolism, including cholesteryl ester transfer protein, lipoprotein lipase, low-density lipoprotein receptor, and apolipoprotein E, have the potential to influence the risk of coronary artery disease [25–27].”
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“Complex interactions between cognitive outcomes and cardiovascular phenotypes such as triglyceride levels [44], arterial thromboembolism, aneurism, and obesity [45] may contribute to attenuated APOE4 effect in individuals with AFR ancestral ancestry.”
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Alagarsamy, J., Jaeschke, A., & Hui, D. Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179892 · Cited by 86
“While some studies showed that ε4 is associated with higher body mass index [105,116], other studies showed no difference between ε3 and ε4 or even opposite results with the ε4 allele associated with reduced obesity [106,117,118].”
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“One plausible mechanism is that APOE ε4 carriers exhibit heightened inflammatory responses to environmental or pathological stressors, including comorbidities such as hypercholesterolemia and ischemic heart disease, to which they are predisposed 65–67 .”
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“A recent phenome-wide association study of APOE genotypes with 950 disease outcomes registered in the UK biobank confirmed the elevated risk of cardiovascular diseases, AD and hypercholesterolaemia associated with ε 4 ( ε 3/ ε 4 or ε 4/ ε 4) compared to the ε 3/ ε 3 genotype [23].”
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“Genomewide genetic data were available for 488,377 participants, of whom 49,950 were genotyped on the UK BiLEVE Axiom array while the remaining were run on the UK Biobank Axiom array [25].”
BackgroundThe Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer’s Disease
Lozupone, M., Dibello, V., Sardone, R., Castellana, F., Zupo, R., Lampignano, L., Bortone, I., Daniele, A., Bellomo, A., Solfrizzi, V., et al. (2023) · Biology · doi:10.3390/biology12121529 · Cited by 39
“Biology 2023 , 12 , 1529 5 Biology 2023 , 12 , x FOR PEER REVIEW 5 of 14 65 [66 In AD, the association between these polymorphic sites and the variability of sequence in the proximal promoter with ApoE protein levels are not clearly understood.”
BackgroundAssociation between liver fibrosis and incident dementia in the UK Biobank study
Parikh, N. S., Kamel, H., Zhang, C., Kumar, S. R., Rosenblatt, R. E., Spincemaille, P., Gupta, A. K., Cohen, D. E., de Leon, M. J., Gottesman, R. F., et al. (2022) · European Journal of Neurology · doi:10.1111/ene.15437 · Cited by 37
“The apolipoprotein gene was directly genotyped for UK Biobank participants, and we used standard definitions to assign genotypes based on rs429358 and rs7412 alleles [31, 32].”
MethodAcute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review
Thong, E. H., Quek, J. W. E., Loo, J. H., Yun, C.-Y., Teo, Y. N., Teo, Y. H., Leow, A. S., Li, T. Y., Sharma, V. K., Tan, B. Y., et al. (2023) · Biology · doi:10.3390/biology12081154 · Cited by 31
“It is also is a prevalent genetic risk factor of AD, being expressed in more than half of AD patients, and this may explain why patients with the ApoE epsilon-4 allele are at increased risk of both AMI and AD [220].”
BackgroundOnisiforou, A., Charalambous, E. G., & Zanos, P. (2025) · Microorganisms · doi:10.3390/microorganisms13010090 · Cited by 32
“The APOE genotype is the most significant genetic risk factor for AD [183].”
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“38,39 In a meta-analysis of studies that reported genotypes and ultrasound examinations, researchers investigated the potential associations between E4 variants and GS disease.”
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“221 The exact mechanisms by which ApoE isoforms contribute to disease pathology, including lipid metabolism, neuroinflammation, synaptic function, and amyloid-beta metabolism in the brain, are still under investigation.”
Innes, H. A., Nischalke, H. D., Guha, I. N., Weiss, K. H., Irving, W. L., Gotthardt, D. N., Barnes, E. J., Fischer, J., Ansari, M. A., Rosendahl, J., et al. (2021) · Hepatology Communications · doi:10.1002/hep4.1886 · Cited by 24
“(24,25) Previous studies have shown that rs429358:C is associated with a reduced risk of cirrhosis in HCV,(25) NAFLD,(8) and in mixed- etiology population cohorts.(26,27) Our results extend this narrative by demonstrating that rs429358:C is also associated with a reduced risk of HCC in HCV cirrhosis, alcohol- related…”
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“The precise pathway by which this variant affects weight change is dif fi cult to pinpoint, as APOE is a highly pleiotropic locus associated with hundreds of biomarkers and diseases 63 .”
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“APOE risk allele frequency for patients and controls was comparable to published series ( Murrell et al., 2006 ; Sando et al., 2008 ; Lumsden et al., 2020 ; Figure 1—figure supplement 1A ), and analysis of germline mutations did not identify deleterious variants in the 140 genes associated with…”
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Kemper, K. E., Sidorenko, J., Wang, H., Hayes, B. J., Wray, N. R., Yengo, L., Keller, M. C., Goddard, M. E., & Visscher, P. M. (2024) · Nature Communications · doi:10.1038/s41467-024-47802-7 · Cited by 21
APOEε4 and risk of Alzheimer’s disease – time to move forward
Lefterov, I. M., Fitz, N. F., Lü, Y., & Koldamova, R. P. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1195724 · Cited by 25
Optimized prime editing of the Alzheimer’s disease-associated APOE4 mutation
Rottner, A. K., Lundin, A., Li, S., Firth, M. A., Maresca, M., & Sienski, G. (2024) · Stem Cell Reports · doi:10.1016/j.stemcr.2024.11.002 · Cited by 23
Murphy, K. B., Hu, D., Wolfs, L., Rohde, S. K., Fauró, G. L., Geric, I., Mancuso, R., De Strooper, B., & Marzi, S. J. (2025) · Nature Communications · doi:10.1038/s41467-025-60099-4 · Cited by 25
Qiao, S.-Y., Shang, K., Chu, Y., Yu, H., Chen, X., Qin, C., Pan, D., & Tian, D.-S. (2022) · Disease Markers · doi:10.1155/2022/1407183 · Cited by 20
“APOE polymorphisms and its risk associations with coronary artery disease [9], hypertension [10], diabetes [11], and carotid arterial atherosclerosis [12] are widely debated.”
BackgroundPitchika, A., Markus, M. R. P., Schipf, S., Teumer, A., der Auwera, S. V., Nauck, M. A., Dörr, M., Felix, S. B., Grabe, H. J., Völzke, H., et al. (2022) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2022.109778 · Cited by 21
Mulugeta, A., Navale, S. S., Lumsden, A. L., Llewellyn, D. J., & Hyppönen, E. (2022) · Nutrients · doi:10.3390/nu14193907 · Cited by 20
“Indeed, one of the key AD variants, APOE4, while increasing the risk in older age disease [31], is also associated with better episodic memory in young and healthy populations [32].”
BackgroundSelf-citationThe Effects of Estrogen on the Risk of Developing Dementia: A Cohort Study Using the UK Biobank Data
Park, H. K., Marston, L., & Mukadam, N. (2024) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2024.01.025 · Cited by 20
Xu, C., Garcia, D., Lu, Y., Ozuna, K., Adjeroh, D. A., Wang, K., & Initiative, O. B. O. T. A. D. N. (2021) · Cells · doi:10.3390/cells11010029 · Cited by 19
“The ApoE ε 3 allele is the most common allele, followed by ε 4 allele [2].”
InfluentialHu, H., Wan, S., Hu, Y., Wang, Q., Li, H., & Zhang, N. (2025) · Annals of Medicine · doi:10.1080/07853890.2024.2445194 · Cited by 20
“Notably, the combination of two non-synonymous single nucleotide polymorphisms (rs429358 and rs7412) in the fourth exon of the APOE gene leads to variations in the amino acids at positions 112 and 158 of the APOE protein [12,13].”
Stephen, T., Breningstall, B. M., Suresh, S., McGill, C. J., & Pike, C. J. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02650-4 · Cited by 17
“Specifically, we find that astrocytes in male E3FAD mice show greater astrocyte coverage, elevated plaque compaction, and lower levels of neurite injury; these effects are significantly diminished by female sex with both APOE3 and APOE4 genotypes.”
BackgroundInfluentialBraak, H., Mayer, B., Feldengut, S., Schön, M., & Tredici, K. D. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02862-x · Cited by 20
Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult
Nunzio, G. D., Hellberg, S., Zhang, Y., Osman, A., Wang, J., Zhang, X., Björck, H. M., Chizh, V., Schipper, R., Aulin, H., et al. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00448-6 · Cited by 19
“APOE also has additional properties beyond lipoprotein transport, including an anti-inflammatory function 18,36 and restraining germinal center formation 18,37 , and human alleles of APOE are implicated in the risk of developing multiple complex diseases, including cardiovascular disease 38 .”
Amyloid-beta metabolism in age-related neurocardiovascular diseases
Aivalioti, E., Georgiopoulos, G. A., Tual‐Chalot, S., Bampatsias, D., Delialis, D., Sopova, K., Drakos, S. G., Stellos, K., & Stamatelopoulos, K. S. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae655 · Cited by 20
“121 Importantly, the observed association of CAD and late-onset AD (LOAD) is mediated by the ApoE locus, and this association vanished when the impact of the ApoE gene is excluded, suggesting that ApoE locus is the chief determinant of shared genetic architecture between CAD and LOAD.”
Taylor, H., Lewins, M., Foody, M. G. B., Gray, O. P., Bešević, J., Conroy, M. C., Collins, R., Lacey, B., Allen, N. E., & Burkitt-Gray, L. (2025) · Neurology Genetics · doi:10.1212/nxg.0000000000200226 · Cited by 18
Baichan, P., Naicker, P., Augustine, T. N., Smith, M., Candy, G. P., Devar, J. W., & Nweke, E. E. (2023) · Clinical Proteomics · doi:10.1186/s12014-023-09399-9 · Cited by 17
Butnariu, L., Gorduza, E., Țarcă, E., Pânzaru, M., Popa, S., Stoleriu, S., Lupu, V., Lupu, A., Cojocaru, E., Trandafir, L., et al. (2023) · Diagnostics · doi:10.3390/diagnostics13142348 · Cited by 16
Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms
Vuić, B., Milos, T., Tudor, L., Perković, M. N., Konjevod, M., Erjavec, G. N., Farkaš, V., Uzun, S., Mimica, N., & Štrac, D. Š. (2023) · Genes · doi:10.3390/genes14112048 · Cited by 17
Gene–Environment Interactions and Stochastic Variations in the Gero-Exposome
Finch, C. E., & Haghani, A. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab045 · Cited by 17
Strafella, C., Caputo, V., Termine, A., Fabrizio, C., Ruffo, P., Potenza, S., Cusumano, A., Ricci, F., Caltagirone, C., Giardina, E., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.626066 · Cited by 16
Heritable confounding of exposure and outcome in Mendelian randomization studiesPreprint
Sanderson, E. C. M., Rosoff, D. B., Vitt, N., Palmer, T., Tilling, K. M., Smith, G. D., & Hemani, G. (2024) · medRxiv · doi:10.1101/2024.09.05.24312293 · Cited by 16
Lower mortality risk in APOE4 carriers with normal cognitive ageing
Pirraglia, E., Glodzik, L., & Shao, Y. (2023) · Scientific Reports · doi:10.1038/s41598-023-41078-5 · Cited by 16
APOE Gene Variation’s Impact on Cardiovascular Health: A Case-Control Study
Ismail, A. B., Balcıoğlu, Ö., Özcem, B., & Ergören, M. Ç. (2024) · Biomedicines · doi:10.3390/biomedicines12030695 · Cited by 15
“In contrast to several preceding studies conducted by Boss et al., 2021 [12], Liu et al., 2019 [41], and Lumsden et al., 2020 [42], which reported a significant positive association between the expression of the ε 4 allele of the APOE gene and cardiovascular diseases.”
ResultInvestigating the Interplay between Cardiovascular and Neurodegenerative Disease
Cousineau, J., Dawe, A. M., & Alpaugh, M. (2024) · Biology · doi:10.3390/biology13100764 · Cited by 15
“For example, mutations in the prese-nilin genes PSEN1 and PSEN2 associated with early familial AD are also associated with dilated cardiomyopathy (CM) and HF [47], while the ApoE4 has also been associated with ischemic heart disease, myocardial infarction (MI), and AS [11,48].”
BackgroundSemaev, S., Шахтшнейдер, Е. В., Щербакова, Л. В., Иванощук, Д. Е., Orlov, P. S., Malyutina, S. K., Гафаров, В. В., Ragino, Y. I., & Voevoda, M. I. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44040118 · Cited by 15
“Judging by the results of major global studies involving UK Biobank data, genotypes ε3/ε4 and ε4/ε4 are associated with hypercholesterolemia and coronary heart disease in contrast to the ε3/ε3 genotype, whereas the ε2/ε3 genotype has shown a protective effect ag inst these pathologi [6].”
BackgroundResultInfluentialApolipoprotein ε in Brain and Retinal Neurodegenerative Diseases
Abyadeh, M., Gupta, V., Paulo, J. A., Sheriff, S., Shadfar, S., Fitzhenry, M. J., Amirkhani, A., Gupta, V. B., Salekdeh, G. H., Haynes, P. A., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0312-1 · Cited by 15
Williams, T., Bathe, T., Vo, Q., Sacilotto, P., McFarland, K. N., Ruiz, A. J., Hery, G. P., Sullivan, P. M., Borchelt, D., Prokop, S., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01581-2 · Cited by 16
“On the other hand, the E2 allele is associated with increased longevity and protection from AD [3], though presence of E2 allele can often lead to hyperlipoproteinemia and metabolic pathologies [4, 5].”
BackgroundCholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage
Huang, R., Pang, Q., Zheng, L., Lin, J., Li, H., Wan, L., & Wang, T. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01462 · Cited by 19
“Furthermore, ApoE ε2 and ε4 are both risk factors for the occurrence of ICH in white populations (Lumsden et al., 2020).”
BackgroundInfluentialPhenome-wide association of APOE alleles in the All of Us Research Program
Khajouei, E., Ghisays, V., Piras, I. S., Martinez, K. L., Vicenti, A. T., Naymik, M., Ngo, P., Tran, T. C., Denny, J. C., Wheeler, T. J., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105768 · Cited by 14
“4,20 In summary, we replicate extensive phenotypic associations with APOE alleles in a large, diverse cohort.”
InfluentialTitcomb, T. J., Richey, P. A., Casanova, R., Phillips, L. S., Liu, S., Karanth, S. D., Saquib, N., Nuño, T., Manson, J. E., Shadyab, A. H., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13416 · Cited by 14
Khaire, A. S., Wimberly, C. E., Semmes, E. C., Hurst, J. H., & Walsh, K. M. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.05.011 · Cited by 13
Cho, S. B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042211 · Cited by 12
Pitchika, A., Markus, M. R. P., Schipf, S., Teumer, A., der Auwera, S. V., Nauck, M. A., Dörr, M., Felix, S. B., Grabe, H. J., Völzke, H., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-09129-5 · Cited by 13
Wu, S., Liu, X., Yang, H., Ma, W., & Qin, Z. (2023) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2023.08.2194 · Cited by 13
“By contrast, the ε 2 allele was often found to be protective, while ε 3 seemed neutral in terms of AD incidence (Lumsden et al., 2020).”
BackgroundPietilä, E. M., Snellman, A., Tuisku, J., Helin, S., Viitanen, M. H., Jula, A., Rinne, J. O., & Ekblad, L. L. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106385 · Cited by 12
“APOE ε 4 genotype is also associated with vascular risk factors (Lumsden et al., 2020) which in turn, often associate with insulin resistance and are also associated with cognitive decline.”
BackgroundAPOE Gene Associated with Cholesterol-Related Traits in the Hispanic Population
Lozano, S., Padilla, V., Avila, M. L., Gil, M., Maestre, G. E., Wang, K., & Xu, C. D. (2021) · Genes · doi:10.3390/genes12111768 · Cited by 12
Affleck, A. J., Sachdev, P. S., & Halliday, G. M. (2023) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12922 · Cited by 11
Huang, X., Han, X., Chang, H., Yu, T., Dong, Y., Mao, M., Ding, J., Li, X., Liu, H., Tian, M., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03166-y · Cited by 11
“We conducted descriptive analyses to examine the characteristics of study participants by sex.”
Data-driven cluster analysis identifies distinct types of cardiovascular-kidney-metabolic syndrome
Yang, M., Su, C., Chang, X., Wang, G., & Liu, J. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf708 · Cited by 11
Wang, Q., Yuan, S., Wang, C., Huang, D., Zhang, M., Zhan, Y., Gao, F., Shi, J., Levey, A. I., & Shen, Y. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01644-z · Cited by 12
Neuropsychiatric symptoms and apolipoprotein E genotypes in neurocognitive disorders
Lozupone, M., Leccisotti, I., Mollica, A., Berardino, G., Moretti, M. C., Altamura, M., Bellomo, A., Daniele, A., Dibello, V., Solfrizzi, V., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01274 · Cited by 11
Chen, J., Chen, H., Wei, Q., Lu, Y., Wang, T., Pang, X., Xing, G., Chen, Z., Cao, X., & Yao, J. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02454-4 · Cited by 11
“The indoor temperature was maintained within a range of 20 – 26 °C, and the humidity was maintained within a range of 40 – 70%.”
Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders
Gilchrist, L., Mutz, J., Hysi, P. G., Legido‐Quigley, C., Kõks, S., Lewis, C. M., & Proitsi, P. (2025) · BMC Medicine · doi:10.1186/s12916-025-04129-4 · Cited by 15
“The APOE region (chr19:45,020,859–45,844,508 (GRCh37)) was excluded from the AD GWAS due to known pleiotropic effects on relevant non-AD diseases such as heart disease and hypercholesterolaemia [54].”
Semaev, S., Шахтшнейдер, Е. В., Щербакова, Л. В., Orlov, P. S., Иванощук, Д. Е., Malyutina, S. K., Гафаров, В. В., Voevoda, M. I., & Ragino, Y. I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310908 · Cited by 11
“In our study, ε3 allele frequencies were consistent with data on the frequency of this allele worldwide [16,30,31].”
BackgroundResultInfluentialJung, J. H., Kong, N., & Lee, S. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100363 · Cited by 10
“The apolipoprotein E ε 4 (APOE4) allele, a well-established genetic risk factor for AD, is associated with vascular damage as well as an increased risk of cardiovascular small vessel disease [16 – 18].”
Fernández‐de‐las‐Peñas, C., Arendt‐Nielsen, L., Díaz‐Gil, G., Gómez‐Esquer, F., Crujera, A. G., Gómez-Sanchez, S. M., Ambite‐Quesada, S., Palomar‐Gallego, M. A., Pellicer-Valero, Ó. J., & Giordano, R. (2023) · Genes · doi:10.3390/genes14071420 · Cited by 10
“observed that the ApoE ε4 genotype is associated with a higher risk of hypercholesterolemia and ischemic heart disease but also with a lower risk (protection effect) of obesity, chronic airway obstruction, and type 2 diabetes, among others [14].”
Background
Metadata
- Authors
- Lumsden, A. L., Mulugeta, A., Zhou, A., & Hyppönen, E.
- Affiliations
- University of South Australia (AU)
- Corresponding author
- Hyppönen, Elina
- Venue
- eBioMedicine
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 59
- Pages
- 102954
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC7452404
- OpenAlex
- W3069395596
- Cited by
- 317
- References
- 31
- Citations by year
- 2026: 54 · 2025: 72 · 2024: 82 · 2023: 59 · 2022: 33 · 2021: 17
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- UK Biobank (GNT1123603)
- National Health and Medical Research Council (GNT1157281)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- apolipoprotein E, APOE genotype, APOE ε4, APOE ε2, Alzheimer's disease, hypercholesterolemia, ischemic heart disease, phenome-wide association study, disease risk, obesity, type 2 diabetes, peripheral vascular disease, thromboembolism, arterial aneurysm, peptic ulcer, hallux valgus, cardiovascular disease, genetic risk factors
- MeSH terms
- Adult, Aged, Alleles, Apolipoproteins E, Female, Genotype, United Kingdom, Humans, Male, Middle Aged, Phenotype, Population Surveillance, Registries, Risk Factors, Case-Control Studies, Biological Specimen Banks, Risk Assessment, Genetic Predisposition to Disease, Genetic Association Studies
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