Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment
Abstract We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)—the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed thei...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02437-y |
| _version_ | 1797836206963163136 |
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| author | Einat Granot-Hershkovitz Brian Spitzer Yunju Yang Wassim Tarraf Bing Yu Eric Boerwinkle Myriam Fornage Thomas H. Mosley Charles DeCarli Bruce S. Kristal Hector M. González Tamar Sofer |
| author_facet | Einat Granot-Hershkovitz Brian Spitzer Yunju Yang Wassim Tarraf Bing Yu Eric Boerwinkle Myriam Fornage Thomas H. Mosley Charles DeCarli Bruce S. Kristal Hector M. González Tamar Sofer |
| author_sort | Einat Granot-Hershkovitz |
| collection | DOAJ |
| description | Abstract We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)—the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value <5 × 10−8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2 gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in the AGXT2 gene and in the SLC6A13 gene. Next, we tested the variants’ association with MCI in independent datasets of n = 3178 HCHS/SOL older individuals, n = 3775 European Americans, and n = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if their p value <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from the AGXT2 region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (p value = 0.004 for causal mediated effect). In summary, genetic variants in the AGXT2 region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels. |
| first_indexed | 2024-04-09T15:06:08Z |
| format | Article |
| id | doaj.art-3c9181d110474b63874021b024adf04f |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-09T15:06:08Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-3c9181d110474b63874021b024adf04f2023-04-30T11:29:05ZengNature Publishing GroupTranslational Psychiatry2158-31882023-04-0113111010.1038/s41398-023-02437-yGenetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairmentEinat Granot-Hershkovitz0Brian Spitzer1Yunju Yang2Wassim Tarraf3Bing Yu4Eric Boerwinkle5Myriam Fornage6Thomas H. Mosley7Charles DeCarli8Bruce S. Kristal9Hector M. González10Tamar Sofer11Division of Sleep and Circadian Disorders, Brigham and Women’s HospitalDivision of Sleep and Circadian Disorders, Brigham and Women’s HospitalBrown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at HoustonInstitute of Gerontology, Wayne State UniversityHuman Genetics Center, School of Public Health University of Texas Health Science Center at HoustonBrown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at HoustonBrown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at HoustonDepartment of Neurology, School of Medicine, University of Mississippi Medical CenterAlzheimerʼs Disease Center, Department of Neurology, University of California, DavisDivision of Sleep and Circadian Disorders, Brigham and Women’s HospitalDepartment of Neurosciences, University of California, San DiegoDivision of Sleep and Circadian Disorders, Brigham and Women’s HospitalAbstract We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)—the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value <5 × 10−8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2 gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in the AGXT2 gene and in the SLC6A13 gene. Next, we tested the variants’ association with MCI in independent datasets of n = 3178 HCHS/SOL older individuals, n = 3775 European Americans, and n = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if their p value <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from the AGXT2 region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (p value = 0.004 for causal mediated effect). In summary, genetic variants in the AGXT2 region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.https://doi.org/10.1038/s41398-023-02437-y |
| spellingShingle | Einat Granot-Hershkovitz Brian Spitzer Yunju Yang Wassim Tarraf Bing Yu Eric Boerwinkle Myriam Fornage Thomas H. Mosley Charles DeCarli Bruce S. Kristal Hector M. González Tamar Sofer Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment Translational Psychiatry |
| title | Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment |
| title_full | Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment |
| title_fullStr | Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment |
| title_full_unstemmed | Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment |
| title_short | Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment |
| title_sort | genetic loci of beta aminoisobutyric acid are associated with aging related mild cognitive impairment |
| url | https://doi.org/10.1038/s41398-023-02437-y |
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