PMID- 36993627
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230806
DP  - 2023 Mar 24
TI  - MAPT allele and haplotype frequencies in Nigerian Africans: population 
      distribution and association with Parkinson's disease risk and age at onset.
LID - 2023.03.24.23287684 [pii]
LID - 10.1101/2023.03.24.23287684 [doi]
AB  - BACKGROUND: The microtubule-associated protein tau ( MAPT ) gene is critical 
      because of its putative role in the causal pathway of neurodegenerative diseases 
      including Parkinson's disease (PD). However, there is a lack of clarity regarding 
      the link between the main H1 haplotype and risk of PD. Inconsistencies in 
      reported association may be driven by genetic variability in the populations 
      studied to date. Data on MAPT haplotype frequencies in the general population and 
      association studies exploring the role of MAPT haplotypes in conferring PD risk 
      in black Africans are lacking. OBJECTIVES: To determine the frequencies of MAPT 
      haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk 
      and age at onset in Nigerian Africans. METHODS: The haplotype and genotype 
      frequencies of MAPT rs1052553 were analysed using PCR-based KASP in 907 
      individuals with PD and 1,022 age-matched neurologically normal controls from the 
      Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related 
      to PD included age at study, age at onset, and disease duration. RESULTS: The 
      frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals 
      with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 
      41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most 
      frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype 
      was not associated with PD risk after accounting for gender and age at onset 
      (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). 
      CONCLUSIONS: Our findings support previous studies that report a low frequency of 
      the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in 
      the Nigerian population (2.1%). In this cohort of black Africans with PD, the 
      MAPT H1 haplotype was not associated with an increased risk or age at onset of 
      PD.
FAU - Okunoye, Olaitan
AU  - Okunoye O
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London WC1N 3BG, United Kingdom.
FAU - Ojo, Oluwadamilola
AU  - Ojo O
AD  - College of Medicine, University of Lagos, and Lagos University Teaching Hospital, 
      Idi Araba, Lagos State, Nigeria.
FAU - Abiodun, Oladunni
AU  - Abiodun O
AD  - General Hospital, Isolo, Lagos State, Nigeria.
FAU - Abubakar, Sani
AU  - Abubakar S
AD  - Ahmadu Bello University, Zaria, Kaduna State, Nigeria.
FAU - Achoru, Charles
AU  - Achoru C
AD  - Jos University Teaching Hospital, Jos, Plateau State, Nigeria.
FAU - Adeniji, Olaleye
AU  - Adeniji O
AD  - Federal Medical Centre, Abeokuta, Ogun State, Nigeria.
FAU - Agabi, Osigwe
AU  - Agabi O
AD  - College of Medicine, University of Lagos, and Lagos University Teaching Hospital, 
      Idi Araba, Lagos State, Nigeria.
FAU - Agulanna, Uchechi
AU  - Agulanna U
AD  - College of Medicine, University of Lagos, and Lagos University Teaching Hospital, 
      Idi Araba, Lagos State, Nigeria.
FAU - Akinyemi, Rufus
AU  - Akinyemi R
AD  - Neuroscience and Ageing Research Unit, Institute for Advanced Medical Research 
      and Training, College of Medicine, University of Ibadan, Ibadan, Oyo State, 
      Nigeria.
FAU - Ali, Mohammed
AU  - Ali M
AD  - Federal Teaching Hospital Gombe, Gombe State, Nigeria.
FAU - Ani-Osheku, Ifeyinwa
AU  - Ani-Osheku I
AD  - Asokoro District Hospital, Asokoro, Abuja, Nigeria.
FAU - Arigbodi, Owotemu
AU  - Arigbodi O
AD  - Delta State University, Abraka, Delta State, Nigeria.
FAU - Bello, Abiodun
AU  - Bello A
AD  - University of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria.
FAU - Erameh, Cyril
AU  - Erameh C
AD  - Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
FAU - Farombi, Temitope
AU  - Farombi T
AD  - University College Hospital, Ibadan, Oyo State, Nigeria.
FAU - Fawale, Michael
AU  - Fawale M
AD  - Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
FAU - Imarhiagbe, Frank
AU  - Imarhiagbe F
AD  - University of Benin, Benin City, Edo State, Nigeria.
FAU - Iwuozo, Emmanuel
AU  - Iwuozo E
AD  - Benue State University, Makurdi, Benue State, Nigeria.
FAU - Komolafe, Morenikeji
AU  - Komolafe M
AD  - Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
FAU - Nwani, Paul
AU  - Nwani P
AD  - Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria.
FAU - Nwazor, Ernest
AU  - Nwazor E
AD  - Rivers State University Teaching Hospital, Port Harcourt, Rivers State, Nigeria.
FAU - Nyandaiti, Yakub
AU  - Nyandaiti Y
AD  - University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria.
FAU - Obiabo, Yahaya
AU  - Obiabo Y
AD  - Federal University of Health Sciences, Otukpo, Benue State, Nigeria.
FAU - Odeniyi, Olanike
AU  - Odeniyi O
AD  - General Hospital, Lagos Island, Lagos State, Nigeria.
FAU - Odiase, Francis
AU  - Odiase F
AD  - University of Benin, Benin City, Edo State, Nigeria.
FAU - Ojini, Francis
AU  - Ojini F
AD  - College of Medicine, University of Lagos, and Lagos University Teaching Hospital, 
      Idi Araba, Lagos State, Nigeria.
FAU - Onwuegbuzie, Gerald
AU  - Onwuegbuzie G
AD  - University of Abuja, Abuja, Federal Capital Territory, Nigeria.
FAU - Osaigbovo, Godwin
AU  - Osaigbovo G
AD  - Jos University Teaching Hospital, Jos, Plateau State, Nigeria.
FAU - Osemwegie, Nosakhare
AU  - Osemwegie N
AD  - University of Port Harcourt, Port Harcourt, Rivers State, Nigeria.
FAU - Oshinaike, Olajumoke
AU  - Oshinaike O
AD  - Lagos State University College of Medicine, Ikeja, Lagos State, Nigeria.
FAU - Otubogun, Folajimi
AU  - Otubogun F
AD  - Federal Medical Center, Ebute Metta, Lagos State, Nigeria.
FAU - Oyakhire, Shyngle
AU  - Oyakhire S
AD  - National Hospital, Abuja, Federal Capital Territory, Nigeria.
FAU - Ozomma, Simon
AU  - Ozomma S
AD  - University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria.
FAU - Samuel, Sarah
AU  - Samuel S
AD  - University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria.
FAU - Taiwo, Funmilola
AU  - Taiwo F
AD  - University College Hospital, Ibadan, Oyo State, Nigeria.
FAU - Wahab, Kolawole
AU  - Wahab K
AD  - University of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria.
FAU - Zubair, Yusuf
AU  - Zubair Y
AD  - National Hospital, Abuja, Federal Capital Territory, Nigeria.
FAU - Hernandez, Dena
AU  - Hernandez D
AD  - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of 
      Health, Bethesda, MD, 20814, USA.
FAU - Bandres-Ciga, Sara
AU  - Bandres-Ciga S
AD  - Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging 
      and National Institute of Neurological Disorders and Stroke, National Institutes 
      of Health, Bethesda, MD, 20814, USA.
FAU - Blauwendraat, Cornelis
AU  - Blauwendraat C
AD  - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of 
      Health, Bethesda, MD, 20814, USA.
AD  - Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging 
      and National Institute of Neurological Disorders and Stroke, National Institutes 
      of Health, Bethesda, MD, 20814, USA.
FAU - Singleton, Andrew
AU  - Singleton A
AD  - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of 
      Health, Bethesda, MD, 20814, USA.
AD  - Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging 
      and National Institute of Neurological Disorders and Stroke, National Institutes 
      of Health, Bethesda, MD, 20814, USA.
FAU - Houlden, Henry
AU  - Houlden H
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London WC1N 3BG, United Kingdom.
FAU - Hardy, John
AU  - Hardy J
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London WC1N 3BG, United Kingdom.
FAU - Rizig, Mie
AU  - Rizig M
AD  - Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, 
      London WC1N 3BG, United Kingdom.
FAU - Okubadejo, Njideka
AU  - Okubadejo N
AUID- ORCID: 0000-0003-2975-8803
AD  - College of Medicine, University of Lagos, and Lagos University Teaching Hospital, 
      Idi Araba, Lagos State, Nigeria.
LA  - eng
GR  - U01 HG010273/HG/NHGRI NIH HHS/United States
GR  - Z01 AG000949/ImNIH/Intramural NIH HHS/United States
PT  - Preprint
DEP - 20230324
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - Parkinsonism Relat Disord. 2023 Jul 14;113:105517. PMID: 37467655
PMC - PMC10055592
COIS- R.A. is supported by the following grants: US NIH/NHGRI (U01HG010273) and the UK 
      Royal Society /African Academy of Sciences (FLR/R1/191813). M.R. received funding 
      from the University College London Grand challenges Small Grants (Award ID:177813 
      and the Michael J Fox Foundation Genetic Diversity in Parkinson's Disease 2019 
      (Grant ID:17483). H.H. is supported by the Michael J Fox Foundation Genetic 
      Diversity in Parkinson's Disease (Grant ID: 17483). N.U.O. is supported by the 
      Michael J Fox Foundation Genetic Diversity in Parkinson's Disease 2019 (Grant 
      ID:17483) and the TETFund National Research Fund (NRF) 2019. S.B.-C., C.B. and 
      A.S. are supported by the Intramural Research Program, National Institute on 
      Aging, National Institutes of Health and US Department of Health and Human 
      Services project ZO1 AG000949 and all these authors declare no non-financial 
      competing interests. The remaining authors declare no competing interests.
EDAT- 2023/03/31 06:00
MHDA- 2023/03/31 06:01
PMCR- 2023/03/29
CRDT- 2023/03/30 02:54
PHST- 2023/03/31 06:01 [medline]
PHST- 2023/03/30 02:54 [entrez]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/29 00:00 [pmc-release]
AID - 2023.03.24.23287684 [pii]
AID - 10.1101/2023.03.24.23287684 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2023 Mar 24:2023.03.24.23287684. doi: 
      10.1101/2023.03.24.23287684.