Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study

Author:

Song Lin123,Han Xiaodong23,Li Yuanjing4,Han Xiaolei23,Zhao Mingqing1,Li Chunyan1,Wang Pin23,Wang Jiafeng23,Dong Yi23,Cong Lin123,Han Xiaojuan123,Hou Tingting123,Liu Keke123,Wang Yongxiang123,Qiu Chengxuan1234,Du Yifeng123ORCID

Affiliation:

1. Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University , 250021 Jinan, Shandong, PR China

2. Department of Neurology , Shandong Provincial Hospital, , 250021 Jinan, Shandong, PR China

3. Shandong University , Shandong Provincial Hospital, , 250021 Jinan, Shandong, PR China

4. Department of Neurobiology, Care Sciences and Society, Aging Research Center and Center for Alzheimer Research, Karolinska Institutet-Stockholm University , 17177 Stockholm, Sweden

Abstract

Abstract The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin’ Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56–0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

Funder

Karolinska Institutet

Swedish Foundation for International Cooperation in Research and Higher Education

Swedish Research Council

Nature Science Foundation of Shandong Province

Taishan Scholar Program of Shandong Province

Academic Promotion Program of Shandong First Medical University

National Nature Science Foundation of China

National Key R&D Program of China

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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