MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinsons disease risk and age at onset.

Abstract

Background: The microtubule-associated protein tau (MAPT) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson 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 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.

Competing Interest Statement

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 Disease 2019 (Grant ID:17483). H.H. is supported by the Michael J Fox Foundation Genetic Diversity in Parkinson Disease (Grant ID: 17483). N.U.O. is supported by the Michael J Fox Foundation Genetic Diversity in Parkinson 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.

Funding Statement

This study was funded by the Michael J Fox Foundation for Parkinson's Research

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The National Health Research Ethics Committee of Nigeria gave ethical approval for this work.

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Yes

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

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