Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring
Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to ex...
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| Veröffentlicht in: | Journal of neurochemistry 2024-03, Vol.168 (3), p.303-311 |
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| description | Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large‐scale genome‐wide association study of maternal history of AD (European‐based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two‐sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave‐one‐out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009–1.018; p |
| doi_str_mv | 10.1111/jnc.16056 |
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The association between maternal history of Alzheimer's disease (AD) and serum cholesterol levels was largely unknown. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable and multivariable MR (MVMR) analyses. Maternal history of AD contributed to hypercholesterolemia and increased levels of total cholesterol and low‐density lipoprotein cholesterol and maternal history of AD was associated with lower levels of high‐density lipoprotein cholesterol in adult offspring. Our results highlight the causal impact of maternal history of AD could serve as an indicator of altered serum cholesterol levels in adult offspring.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/jnc.16056</identifier><identifier>PMID: 38316937</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Alzheimer's disease ; causal inference ; Cholesterol ; Density ; Diabetes mellitus ; family history ; Genetic diversity ; Genetic variance ; Genomes ; Hypercholesterolemia ; Mendelian randomization ; Neurodegenerative diseases ; Nucleotides ; Observational studies ; Offspring ; Statistical analysis</subject><ispartof>Journal of neurochemistry, 2024-03, Vol.168 (3), p.303-311</ispartof><rights>2024 International Society for Neurochemistry.</rights><rights>Copyright © 2024 International Society for Neurochemistry</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3136-e5589c5c12b1d2645e1f896672a2eef83c9c19f0bd7daed04d6441cfb41ac1f43</cites><orcidid>0000-0002-3154-6909 ; 0000-0002-2180-2235</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjnc.16056$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjnc.16056$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38316937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Yuehui</creatorcontrib><creatorcontrib>Deng, Ming‐Gang</creatorcontrib><creatorcontrib>Jian, Qinghong</creatorcontrib><creatorcontrib>Liu, Mingwei</creatorcontrib><creatorcontrib>Fang, Kui</creatorcontrib><creatorcontrib>Chen, Shuai</creatorcontrib><title>Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large‐scale genome‐wide association study of maternal history of AD (European‐based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two‐sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave‐one‐out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009–1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134–1.466; p < 0.001) and low‐density lipoprotein (OR = 1.525; 95% CI: 1.272–1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high‐density lipoprotein (OR = 0.889; 95% CI: 0.861–0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.
The association between maternal history of Alzheimer's disease (AD) and serum cholesterol levels was largely unknown. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable and multivariable MR (MVMR) analyses. Maternal history of AD contributed to hypercholesterolemia and increased levels of total cholesterol and low‐density lipoprotein cholesterol and maternal history of AD was associated with lower levels of high‐density lipoprotein cholesterol in adult offspring. Our results highlight the causal impact of maternal history of AD could serve as an indicator of altered serum cholesterol levels in adult offspring.</description><subject>Alzheimer's disease</subject><subject>causal inference</subject><subject>Cholesterol</subject><subject>Density</subject><subject>Diabetes mellitus</subject><subject>family history</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Genomes</subject><subject>Hypercholesterolemia</subject><subject>Mendelian randomization</subject><subject>Neurodegenerative diseases</subject><subject>Nucleotides</subject><subject>Observational studies</subject><subject>Offspring</subject><subject>Statistical analysis</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kU2PFCEQhonRuOPqwT9gSDyoh96lgKab42biZ1a96LnDQOH0hG5Galoz_nrZndWDiVwglYcHql7GnoK4gLoud7O_ACNac4-tQHfQaGjtfbYSQspGCS3P2COinRBgtIGH7Ez1CoxV3YrtProDltklvh3pkMuR58iv0q8tjhOWF8TDSOgI-b5gPe4zIfFD5i7Vaxg4YVkm7rc5IdVKTjzhD0zEx5m7sKRD9UXal3H-9pg9iC4RPrnbz9nXN6-_rN8115_fvl9fXTdegTINtm1vfetBbiBIo1uE2FtjOukkYuyVtx5sFJvQBYdB6GC0Bh83GpyHqNU5e3ny7kv-vtRvDdNIHlNyM-aFBmmltLrrRF_R5_-gu7zcTOOWqo8qq2WlXp0oXzJRwTjUfiZXjgOI4SaAoQYw3AZQ2Wd3xmUzYfhL_pl4BS5PwM8x4fH_puHDp_VJ-Ruj-JCX</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Liang, Yuehui</creator><creator>Deng, Ming‐Gang</creator><creator>Jian, Qinghong</creator><creator>Liu, Mingwei</creator><creator>Fang, Kui</creator><creator>Chen, Shuai</creator><general>Blackwell Publishing Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3154-6909</orcidid><orcidid>https://orcid.org/0000-0002-2180-2235</orcidid></search><sort><creationdate>202403</creationdate><title>Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring</title><author>Liang, Yuehui ; Deng, Ming‐Gang ; Jian, Qinghong ; Liu, Mingwei ; Fang, Kui ; Chen, Shuai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3136-e5589c5c12b1d2645e1f896672a2eef83c9c19f0bd7daed04d6441cfb41ac1f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alzheimer's disease</topic><topic>causal inference</topic><topic>Cholesterol</topic><topic>Density</topic><topic>Diabetes mellitus</topic><topic>family history</topic><topic>Genetic diversity</topic><topic>Genetic variance</topic><topic>Genomes</topic><topic>Hypercholesterolemia</topic><topic>Mendelian randomization</topic><topic>Neurodegenerative diseases</topic><topic>Nucleotides</topic><topic>Observational studies</topic><topic>Offspring</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liang, Yuehui</creatorcontrib><creatorcontrib>Deng, Ming‐Gang</creatorcontrib><creatorcontrib>Jian, Qinghong</creatorcontrib><creatorcontrib>Liu, Mingwei</creatorcontrib><creatorcontrib>Fang, Kui</creatorcontrib><creatorcontrib>Chen, Shuai</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liang, Yuehui</au><au>Deng, Ming‐Gang</au><au>Jian, Qinghong</au><au>Liu, Mingwei</au><au>Fang, Kui</au><au>Chen, Shuai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2024-03</date><risdate>2024</risdate><volume>168</volume><issue>3</issue><spage>303</spage><epage>311</epage><pages>303-311</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large‐scale genome‐wide association study of maternal history of AD (European‐based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two‐sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave‐one‐out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009–1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134–1.466; p < 0.001) and low‐density lipoprotein (OR = 1.525; 95% CI: 1.272–1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high‐density lipoprotein (OR = 0.889; 95% CI: 0.861–0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.
The association between maternal history of Alzheimer's disease (AD) and serum cholesterol levels was largely unknown. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable and multivariable MR (MVMR) analyses. Maternal history of AD contributed to hypercholesterolemia and increased levels of total cholesterol and low‐density lipoprotein cholesterol and maternal history of AD was associated with lower levels of high‐density lipoprotein cholesterol in adult offspring. Our results highlight the causal impact of maternal history of AD could serve as an indicator of altered serum cholesterol levels in adult offspring.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>38316937</pmid><doi>10.1111/jnc.16056</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3154-6909</orcidid><orcidid>https://orcid.org/0000-0002-2180-2235</orcidid></addata></record> |
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| subjects | Alzheimer's disease causal inference Cholesterol Density Diabetes mellitus family history Genetic diversity Genetic variance Genomes Hypercholesterolemia Mendelian randomization Neurodegenerative diseases Nucleotides Observational studies Offspring Statistical analysis |
| title | Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring |
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