A locus at 19q13.31 significantly reduces the <em>ApoE</em> ε4 risk for Alzheimer\u27s Disease in African Ancestry

Copyright: \ua9 2022 Rajabli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. African descent populations have a lower Alzheimer disease risk from ApoE ε4 compared to other populations. Ancestry analysis showed that the difference in risk between African and European populations lies in the ancestral genomic background surrounding the ApoE locus (local ancestry). Identifying the mechanism(s) of this protection could lead to greater insight into the etiology of Alzheimer disease and more personalized therapeutic intervention. Our objective is to follow up the local ancestry finding and identify the genetic variants that drive this risk difference and result in a lower risk for developing Alzheimer disease in African ancestry populations. We performed association analyses using a logistic regression model with the ApoE ε4 allele as an interaction term and adjusted for genome-wide ancestry, age, and sex. Discovery analysis included imputed SNP data of 1,850 Alzheimer disease and 4,331 cognitively intact African American individuals. We performed replication analyses on 63 whole genome sequenced Alzheimer disease and 648 cognitively intact Ibadan individuals. Additionally, we reproduced results using whole-genome sequencing of 273 Alzheimer disease and 275 cognitively intact admixed Puerto Rican individuals. A further comparison was done with SNP imputation from an additional 8,463 Alzheimer disease and 11,365 cognitively intact non-Hispanic White individuals. We identified a significant interaction between the ApoE ε4 allele and the SNP rs10423769_A allele, (β = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (β = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (β = -1.27,SE = 0.64,p-value = 4.91x10-2) individuals. The non-Hispanic Whites analyses showed an interaction trending in the “protective” direction but failing to pass a 0.05 significance threshold (β = -1.51,SE = 0.84,p-value = 7.26x10-2). The presence of the rs10423769_A allele reduces the odds ratio for Alzheimer disease risk from 7.2 for ApoE ε4/ε4 carriers lacking the A allele to 2.1 for ApoE ε4/ε4 carriers with at least one A allele. This locus is located approximately 2 mB upstream of the ApoE locus, in a large cluster of pregnancy specific beta-1 glycoproteins on chromosome 19 and lies within a long noncoding RNA, ENSG00000282943. This study identified a new African-ancestry specific locus that reduces the risk effect of ApoE ε4 for developing Alzheimer disease. The mechanism of the interaction with ApoEε4 is not known but suggests a novel mechanism for reducing the risk for ε4 carriers opening the possibility for potential ancestry-specific therapeutic intervention

Resonant magnetoabsorption of millimeter-wave radiation in the quasi-two-dimensional organic metals alpha -(BEDT-TTF)2MHg(SCN)4 (M=K,Tl).

The magnetoabsorption of millimeter-wave radiation by single crystals of the organic metals α-(BEDT-TTF)2TlHg(SCN)4 and α-(BEDT-TTF)2KHg(SCN)4 has been studied in the frequency range 30-120 GHz. The experiments reveal two dominant contributions to the magnetoabsorption spectra. The first is interpreted as the cyclotron resonance of two-dimensional carriers, and is characterized by broad lines (linewidth/magnetic field ΔB/B∼0.5-1). In addition to a resonance exhibiting a cyclotron mass mc∼2.8m0, there are two further lines corresponding to frequency-dependent cyclotron masses in the ranges mc∼(1-1.5)m0 and mc∼(0.5-0.8)m0. This frequency dependence is believed to result from many-body effects. The second contribution to the magnetoabsorption is formed by a series of narrow lines with ΔB/B∼0.03-0.1 and amplitudes 5-10 times smaller than the features interpreted as cyclotron resonances. These narrow lines are attributed to a superposition of modes due to antiferromagnetic resonance and conduction-electron-spin resonance (ESR). The feature characteristic of antiferromagnetic resonance is the presence of a mode with a frequency that decreases with increasing magnetic field. The magnetoabsorption structure attributed to ESR consists of a relatively broad maximum upon which a sharp dip is superimposed. This behavior is believed to be analogous to the resonant transparency observed in thin metallic films undergoing ESR