Polygenic effects on the risk of Alzheimer's disease in the Japanese population.

Alzheimer’s disease Mild cognitive impairment Polygenic risk score

Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
27 Feb 2024
Historique:
received: 10 08 2023
accepted: 11 02 2024
medline: 28 2 2024
pubmed: 28 2 2024
entrez: 28 2 2024
Statut: epublish

Résumé

Polygenic effects have been proposed to account for some disease phenotypes; these effects are calculated as a polygenic risk score (PRS). This score is correlated with Alzheimer's disease (AD)-related phenotypes, such as biomarker abnormalities and brain atrophy, and is associated with conversion from mild cognitive impairment (MCI) to AD. However, the AD PRS has been examined mainly in Europeans, and owing to differences in genetic structure and lifestyle, it is unclear whether the same relationships between the PRS and AD-related phenotypes exist in non-European populations. In this study, we calculated and evaluated the AD PRS in Japanese individuals using genome-wide association study (GWAS) statistics from Europeans. In this study, we calculated the AD PRS in 504 Japanese participants (145 cognitively unimpaired (CU) participants, 220 participants with late mild cognitive impairment (MCI), and 139 patients with mild AD dementia) enrolled in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) project. In order to evaluate the clinical value of this score, we (1) determined the polygenic effects on AD in the J-ADNI and validated it using two independent cohorts (a Japanese neuropathology (NP) cohort (n = 565) and the North American ADNI (NA-ADNI) cohort (n = 617)), (2) examined the AD-related phenotypes associated with the PRS, and (3) tested whether the PRS helps predict the conversion of MCI to AD. The PRS using 131 SNPs had an effect independent of APOE. The PRS differentiated between CU participants and AD patients with an area under the curve (AUC) of 0.755 when combined with the APOE variants. Similar AUC was obtained when PRS calculated by the NP and NA-ADNI cohorts was applied. In MCI patients, the PRS was associated with cerebrospinal fluid phosphorylated-tau levels (β estimate = 0.235, p value = 0.026). MCI with a high PRS showed a significantly increased conversion to AD in APOE ε4 noncarriers with a hazard rate of 2.22. In addition, we also developed a PRS model adjusted for LD and observed similar results. We showed that the AD PRS is useful in the Japanese population, whose genetic structure is different from that of the European population. These findings suggest that the polygenicity of AD is partially common across ethnic differences.

Sections du résumé

BACKGROUND BACKGROUND
Polygenic effects have been proposed to account for some disease phenotypes; these effects are calculated as a polygenic risk score (PRS). This score is correlated with Alzheimer's disease (AD)-related phenotypes, such as biomarker abnormalities and brain atrophy, and is associated with conversion from mild cognitive impairment (MCI) to AD. However, the AD PRS has been examined mainly in Europeans, and owing to differences in genetic structure and lifestyle, it is unclear whether the same relationships between the PRS and AD-related phenotypes exist in non-European populations. In this study, we calculated and evaluated the AD PRS in Japanese individuals using genome-wide association study (GWAS) statistics from Europeans.
METHODS METHODS
In this study, we calculated the AD PRS in 504 Japanese participants (145 cognitively unimpaired (CU) participants, 220 participants with late mild cognitive impairment (MCI), and 139 patients with mild AD dementia) enrolled in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) project. In order to evaluate the clinical value of this score, we (1) determined the polygenic effects on AD in the J-ADNI and validated it using two independent cohorts (a Japanese neuropathology (NP) cohort (n = 565) and the North American ADNI (NA-ADNI) cohort (n = 617)), (2) examined the AD-related phenotypes associated with the PRS, and (3) tested whether the PRS helps predict the conversion of MCI to AD.
RESULTS RESULTS
The PRS using 131 SNPs had an effect independent of APOE. The PRS differentiated between CU participants and AD patients with an area under the curve (AUC) of 0.755 when combined with the APOE variants. Similar AUC was obtained when PRS calculated by the NP and NA-ADNI cohorts was applied. In MCI patients, the PRS was associated with cerebrospinal fluid phosphorylated-tau levels (β estimate = 0.235, p value = 0.026). MCI with a high PRS showed a significantly increased conversion to AD in APOE ε4 noncarriers with a hazard rate of 2.22. In addition, we also developed a PRS model adjusted for LD and observed similar results.
CONCLUSIONS CONCLUSIONS
We showed that the AD PRS is useful in the Japanese population, whose genetic structure is different from that of the European population. These findings suggest that the polygenicity of AD is partially common across ethnic differences.

Identifiants

pubmed: 38414085
doi: 10.1186/s13195-024-01414-x
pii: 10.1186/s13195-024-01414-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

45

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 20K15778
Organisme : Japan Society for the Promotion of Science
ID : 21K07271
Organisme : Japan Society for the Promotion of Science
ID : 22H04923
Organisme : Japan Agency for Medical Research and Development
ID : JP21dk0207045
Organisme : Japan Agency for Medical Research and Development
ID : JP21dk0207045
Organisme : Japan Agency for Medical Research and Development
ID : JP21wm0425019
Organisme : Japan Agency for Medical Research and Development
ID : JP21dk0207045
Organisme : Japan Agency for Medical Research and Development
ID : JP21dk0207045
Organisme : Japan Agency for Medical Research and Development
ID : JP21dk0207045
Organisme : Grants-in Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan
ID : 20FC1049

Investigateurs

Michael W Weiner (MW)
Sara S Mason (SS)
Colleen S Albers (CS)
David Knopman (D)
Kris Johnson (K)
Paul Aisen (P)
Ronald Petersen (R)
Clifford R Jack (CR)
William Jagust (W)
John Q Trojanowki (JQ)
Arthur W Toga (AW)
Lon S Schneider (LS)
Sonia Pawluczyk (S)
Mauricio Beccera (M)
Liberty Teodoro (L)
Bryan M Spann (BM)
Laurel Beckett (L)
Robert C Green (RC)
John Morris (J)
Leslie M Shaw (LM)
Beau Ances (B)
John C Morris (JC)
Maria Carroll (M)
Mary L Creech (ML)
Erin Franklin (E)
Mark A Mintun (MA)
Stacy Schneider (S)
Angela Oliver (A)
Jeffrey Kaye (J)
Joseph Quinn (J)
Lisa Silbert (L)
Betty Lind (B)
Raina Carter (R)
Sara Dolen (S)
James Brewer (J)
Helen Vanderswag (H)
Adam Fleisher (A)
Judith L Heidebrink (JL)
Joanne L Lord (JL)
Rachelle S Doody (RS)
Javier Villanueva-Meyer (J)
Munir Chowdhury (M)
Susan Rountree (S)
Mimi Dang (M)
Yaakov Stern (Y)
Lawrence S Honig (LS)
Karen L Bell (KL)
Daniel Marson (D)
Randall Griffith (R)
David Clark (D)
David Geldmacher (D)
John Brockington (J)
Erik Roberson (E)
Marissa Natelson Love (MN)
Hillel Grossman (H)
Effie Mitsis (E)
Raj C Shah (RC)
Leyla deToledo-Morrell (L)
Ranjan Duara (R)
Daniel Varon (D)
Maria T Greig (MT)
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Chiadi Onyike (C)
Daniel D'Agostino (D)
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Motokatsu Kanemoto (M)
Jun Takeuchi (J)
Rie Azuma (R)
Naomi Tagawa (N)
Junko Masao (J)
Yuka Matsumoto (Y)
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Hisako Fujii (H)
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Taichi Akisaki (T)
Mizuho Adachi (M)
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Yatsuka Okada (Y)
Tomomi Ogihara (T)
Toru Takahashi (T)
Shin Inuzuka (S)
Nobuhiro Sugiyama (N)
Takehiko Yasaki (T)
Minori Kitayama (M)
Tomonori Owa (T)
Akiko Ryokawa (A)
Rie Takeuchi (R)
Satoe Goto (S)
Keiko Yamauchi (K)
Mie Ito (M)
Tomoki Kaneko (T)
Hitoshi Ueda (H)
Shuichi Ikeda (S)
Ban Mihara (B)
Hirofumi Kubo (H)
Akiko Takano (A)
Gou Yasui (G)
Masami Akuzawa (M)
Kaori Yamaguchi (K)
Toshinari Odawara (T)
Naomi Oota (N)
Megumi Shimamura (M)
Mikiko Sugiyama (M)
Atsushi Watanabe (A)
Shigeo Takebayashi (S)
Yoshigazu Hayakawa (Y)
Mitsuhiro Idegawa (M)
Noriko Toya (N)
Kazunari Ishii (K)

Informations de copyright

© 2024. The Author(s).

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Auteurs

Masataka Kikuchi (M)

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, 6-2-3 Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan. kikuchi@edu.k.u-tokyo.ac.jp.
Department of Medical Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan. kikuchi@edu.k.u-tokyo.ac.jp.

Akinori Miyashita (A)

Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8585, Japan.

Norikazu Hara (N)

Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8585, Japan.

Kensaku Kasuga (K)

Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8585, Japan.

Yuko Saito (Y)

Brain Bank for Aging Research (Department of Neuropathology), Tokyo Metropolitan Institute of Geriatrics and Gerontology, Tokyo, Japan.

Shigeo Murayama (S)

Brain Bank for Aging Research (Department of Neuropathology), Tokyo Metropolitan Institute of Geriatrics and Gerontology, Tokyo, Japan.
Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University, Osaka, Japan.

Akiyoshi Kakita (A)

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

Hiroyasu Akatsu (H)

Department of General Medicine & General Internal Medicine, Nagoya City University Graduate School of Medicine, Nagoya, Japan.

Kouichi Ozaki (K)

Medical Genome Center, National Center for Geriatrics and Gerontology, Research Institute, Aichi, Japan.
RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Shumpei Niida (S)

Core Facility Administration, National Center for Geriatrics and Gerontology, Research Institute, Aichi, Japan.

Ryozo Kuwano (R)

Social Welfare Corporation Asahigawaso, Asahigawaso Research Institute, Okayama, Japan.

Takeshi Iwatsubo (T)

Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Akihiro Nakaya (A)

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, 6-2-3 Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.

Takeshi Ikeuchi (T)

Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951-8585, Japan. ikeuchi@bri.niigata-u.ac.jp.

Classifications MeSH