Browsing by Subject "European ancestry"

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    Association between known Alzheimer’s disease risk genetic variants and hippocampal atrophy along the Alzheimer’s disease continuum in a Korean cohort
    (Wiley, 2025-01-03) Ahn, Hyejin; Byun, Min Soo; Yi, Dahyun; Jung, Gijung; Huang, Yen-Ning; Risacher, Shannon L.; Griswold, Anthony J.; Pericak-Vance, Margaret A.; Kim, Yu Kyeong; Lee, Yun-Sang; Sohn, Chul-Ho; Kang, Koung Mi; Lee, Jun-Young; Saykin, Andrew J.; Nho, Kwangsik; Lee, Dong Young; Radiology and Imaging Sciences, School of Medicine
    Background: Large‐scale genome‐wide association studies (GWAS) of Alzheimer’s disease (AD) from European ancestry identified many genetic variants associated with clinical diagnosis of AD dementia. However, it remains unclear whether these AD‐related variants are associated with AD biomarkers, particularly hippocampal atrophy, a well‐known neurodegeneration biomarker of AD in a Korean population. In this study, we investigated the association between known AD risk single nucleotide polymorphisms (SNPs) and hippocampal atrophy along the AD continuum in older Korean adults. Method: A total of 487 participants (258 cognitively normal olde adults [CN], 144 mild cognitive impairment [MCI], 85 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE) were included for analysis. All participants underwent 11C‐PiB‐PET/MRI. Hippocampal volume adjusted for intracranial volume (HVa) was obtained from 3D T1‐weighted MRI scans using FreeSurfer and used as a neurodegeneration marker of AD. Global beta‐amyloid (Aβ) deposition was calculated from PiB uptake in the global cortical region‐of‐interest using SPM12. From the genetic evidence gathered by the AD Sequencing Project (ADSP), which consists of 76 SNPs associated with AD, we selected 38 SNPs with a minor allele frequency (MAF) greater than 1% from the genotyping data imputed using the TOPMed imputation server in the KBASE cohort. Result: Among 38 known AD‐related SNPs, three SNPs (rs6966331 in EPDR1, rs2242595 in MYO15A, and rs17125924 in FERMT2) were associated with HVa in an initial exploratory analysis (p<0.05). In a subsequent confirmatory analysis, the associations of rs6966331 in EPDR1 and rs2242595 in MYO15A with HVa remained significant after controlling for age, sex, and APOE4 carrier status, as well as global Aβ deposition (p<0.001 and p = 0.009 for rs6966331 and rs2242595, respectively) (Table 1). Conclusion: Our study identified associations of rs6966331 in EPDR1 and rs2242595 in MYO15A with hippocampal volume in Korean older adults, and these associations were independent of cerebral Aβ deposition and APOE4 carrier status. These findings suggest that these AD‐related loci may contribute to the development of AD dementia via Aβ‐independent neurodegeneration.
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    Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure
    (Nature Publishing Group, 2018-05-08) Visconti, Alessia; Duffy, David L.; Liu, Fan; Zhu, Gu; Wu, Wenting; Chen, Yan; Hysi, Pirro G.; Zeng, Changqing; Sanna, Marianna; Iles, Mark M.; Kanetsky, Peter A.; Demenais, Florence; Hamer, Merel A.; Uitterlinden, Andre G.; Ikram, M. Arfan; Nijsten, Tamar; Martin, Nicholas G.; Kayser, Manfred; Spector, Tim D.; Han, Jiali; Bataille, Veronique; Falchi, Mario; Epidemiology, School of Public Health
    The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.
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    Racial Differences in Predictive Capacity of Educational Polygenic Scores on Physical Limitations for Older Adults
    (Oxford University Press, 2024-12-31) Catt, Wade; Williams, Micah; Latham-Mintus, Kenzie; Medicine, School of Medicine
    This research examined whether educational polygenic scores were associated with physical limitations among older adults with European or African ancestry. In the European ancestry sample, we found that education polygenic scores were significantly associated with physical limitations in the age- and sex-adjusted models; however, education polygenic scores were no longer associated with physical limitations after adjusting for current socioeconomic status and health risk factors. In the African ancestry sample, education polygenic scores were not associated with physical limitations. Observed educational attainment was a robust predictor of physical limitations in both samples. This research demonstrates the racial inequalities in the predictive capacity of educational polygenic scores. We hypothesize that this disparity is a result of structural barriers to educational attainment by race and/or racial inequities in data collection. Both explanations stem from structural racism and highlight the limited usefulness of polygenic scores for clinical decision-making. We use these findings to explore competing theoretical explanatory frameworks of the utility and limitations of the use of polygenic scores in social and health sciences.