A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA)...
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Autor*in:	Sofer, Tamar [verfasserIn] Kurniansyah, Nuzulul Granot-Hershkovitz, Einat Goodman, Matthew O. Tarraf, Wassim Broce, Iris Lipton, Richard B. Daviglus, Martha Lamar, Melissa Wassertheil-Smoller, Sylvia Cai, Jianwen DeCarli, Charles S. Gonzalez, Hector M. Fornage, Myriam

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Admixture Diverse populations Polygenic risk score Mild cognitive impairment Cognitive decline

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Alzheimer's research & therapy - London : BioMed Central, 2009, 15(2023), 1 vom: 30. Aug.
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:1 ; day:30 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s13195-023-01298-3

Katalog-ID:	SPR052929957

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245	1	2	\|a A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
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520			\|a Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.
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allfields	10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08
spelling	10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08
allfields_unstemmed	10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08
allfieldsGer	10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08
allfieldsSound	10.1186/s13195-023-01298-3 doi (DE-627)SPR052929957 (SPR)s13195-023-01298-3-e DE-627 ger DE-627 rakwb eng Sofer, Tamar verfasserin aut A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213 Kurniansyah, Nuzulul aut Granot-Hershkovitz, Einat aut Goodman, Matthew O. aut Tarraf, Wassim aut Broce, Iris aut Lipton, Richard B. aut Daviglus, Martha aut Lamar, Melissa aut Wassertheil-Smoller, Sylvia aut Cai, Jianwen aut DeCarli, Charles S. aut Gonzalez, Hector M. aut Fornage, Myriam aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 15(2023), 1 vom: 30. Aug. (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:15 year:2023 number:1 day:30 month:08 https://dx.doi.org/10.1186/s13195-023-01298-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 30 08
language	English
source	Enthalten in Alzheimer's research & therapy 15(2023), 1 vom: 30. Aug. volume:15 year:2023 number:1 day:30 month:08
sourceStr	Enthalten in Alzheimer's research & therapy 15(2023), 1 vom: 30. Aug. volume:15 year:2023 number:1 day:30 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Admixture Diverse populations Polygenic risk score Mild cognitive impairment Cognitive decline
isfreeaccess_bool	true
container_title	Alzheimer's research & therapy
authorswithroles_txt_mv	Sofer, Tamar @@aut@@ Kurniansyah, Nuzulul @@aut@@ Granot-Hershkovitz, Einat @@aut@@ Goodman, Matthew O. @@aut@@ Tarraf, Wassim @@aut@@ Broce, Iris @@aut@@ Lipton, Richard B. @@aut@@ Daviglus, Martha @@aut@@ Lamar, Melissa @@aut@@ Wassertheil-Smoller, Sylvia @@aut@@ Cai, Jianwen @@aut@@ DeCarli, Charles S. @@aut@@ Gonzalez, Hector M. @@aut@@ Fornage, Myriam @@aut@@
publishDateDaySort_date	2023-08-30T00:00:00Z
hierarchy_top_id	605683557
id	SPR052929957
language_de	englisch
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Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. 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author	Sofer, Tamar
spellingShingle	Sofer, Tamar misc Admixture misc Diverse populations misc Polygenic risk score misc Mild cognitive impairment misc Cognitive decline A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
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topic_title	A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. Admixture (dpeaa)DE-He213 Diverse populations (dpeaa)DE-He213 Polygenic risk score (dpeaa)DE-He213 Mild cognitive impairment (dpeaa)DE-He213 Cognitive decline (dpeaa)DE-He213
topic	misc Admixture misc Diverse populations misc Polygenic risk score misc Mild cognitive impairment misc Cognitive decline
topic_unstemmed	misc Admixture misc Diverse populations misc Polygenic risk score misc Mild cognitive impairment misc Cognitive decline
topic_browse	misc Admixture misc Diverse populations misc Polygenic risk score misc Mild cognitive impairment misc Cognitive decline
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title	A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
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title_full	A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
author_sort	Sofer, Tamar
journal	Alzheimer's research & therapy
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author_browse	Sofer, Tamar Kurniansyah, Nuzulul Granot-Hershkovitz, Einat Goodman, Matthew O. Tarraf, Wassim Broce, Iris Lipton, Richard B. Daviglus, Martha Lamar, Melissa Wassertheil-Smoller, Sylvia Cai, Jianwen DeCarli, Charles S. Gonzalez, Hector M. Fornage, Myriam
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author-letter	Sofer, Tamar
doi_str_mv	10.1186/s13195-023-01298-3
title_sort	polygenic risk score for alzheimer’s disease constructed using apoe-region variants has stronger association than apoe alleles with mild cognitive impairment in hispanic/latino adults in the u.s.
title_auth	A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
abstract	Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023
abstractGer	Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023
abstract_unstemmed	Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-%$\epsilon 2%$ and APOE-%$\epsilon 4%$ alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-%$\epsilon 4%$ and APOE-%$\epsilon 2%$ alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults. © The Author(s) 2023
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title_short	A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
url	https://dx.doi.org/10.1186/s13195-023-01298-3
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author2	Kurniansyah, Nuzulul Granot-Hershkovitz, Einat Goodman, Matthew O. Tarraf, Wassim Broce, Iris Lipton, Richard B. Daviglus, Martha Lamar, Melissa Wassertheil-Smoller, Sylvia Cai, Jianwen DeCarli, Charles S. Gonzalez, Hector M. Fornage, Myriam
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A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

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