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우수성과SAIHST 구성원의 언론보도내용 및 수상내역, 각 연구분야의 우수 학술지에 게재된 논문 등 우수한 성과들을 소개합니다.

[원홍희 교수/ 우수논문] Brain. 06 October 2021
No 87
작성자 관리자
등록일 2022/04/18

 

책임저자

 



원홍희 교수

삼성융합의과학원

 

 

Impact Factor('21)= 13.501 

 

Brain. 06 October 2021, https://doi.org/10.1093/brain/awab351


Genome-wide association study of occupational attainment as a proxy for cognitive reserve 
Hyunwoong Ko, Soyeon Kim,  Kiwon Kim,  Sang-Hyuk Jung, Injeong Shim, Soojin Cha, Hyewon Lee, Beomsu Kim, Joohyun Yoon, Tae Hyon Ha, Seyul Kwak, Jae Myeong Kang, Jun-Young Lee, Jinho Kim, Woong-Yang Park, Kwangsik Nho, Doh Kwan Kim, Woojae Myung, Hong-Hee Won


Abstract

Occupational attainment, which represents middle-age cognitive activities, is a known proxy marker of cognitive reserve for Alzheimer's disease. Previous genome-wide association studies have identified numerous genetic variants and revealed the genetic architecture of educational attainment, another marker of cognitive reserve. However, the genetic architecture and heritability for occupational attainment remain elusive.

We performed a large-scale genome-wide association study of occupational attainment with 248 847 European individuals from the UK Biobank using the proportional odds logistic mixed model method. In this analysis, we defined occupational attainment using the classified job levels formulated in the UK Standard Occupational Classification system considering the individual professional skill and academic level.

We identified 30 significant loci (P < 5 × 10−8); 12 were novel variants, not associated with other traits. Among them, four lead variants were associated with genes expressed in brain tissues by expression quantitative trait loci mapping from 10 brain regions: rs13002946, rs3741368, rs11654986 and rs1627527. The single nucleotide polymorphism-based heritability was estimated to be 8.5% (standard error of the mean = 0.004) and partitioned heritability was enriched in the CNS and brain tissues. Genetic correlation analysis showed shared genetic backgrounds between occupational attainment and multiple traits, including education, intelligence, leisure activities, life satisfaction and neuropsychiatric disorders. In two-sample Mendelian randomization analysis, we demonstrated that high occupation levels were associated with reduced risk for Alzheimer's disease [odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65–0.92 in inverse variance weighted method; OR = 0.73, 95% CI = 0.57–0.92 in the weighted median method]. This causal relationship between occupational attainment and Alzheimer's disease was robust in additional sensitivity analysis that excluded potentially pleiotropic single nucleotide polymorphisms (OR = 0.72, 95% CI = 0.57–0.91 in the inverse variance weighted method; OR = 0.72, 95% CI = 0.53–0.97 in the weighted median method). Multivariable Mendelian randomization confirmed that occupational attainment had an independent effect on the risk for Alzheimer’s disease even after taking educational attainment into account (OR = 0.72, 95% CI = 0.54–0.95 in the inverse variance weighted method; OR = 0.68, 95% CI = 0.48–0.97 in the weighted median method).

Overall, our analyses provide insights into the genetic architecture of occupational attainment and demonstrate that occupational attainment is a potential causal protective factor for Alzheimer's disease as a proxy marker of cognitive reserve.

 

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