Browsing by Author "Aiello, AE"

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    Investigating pathogen burden in relation to a cumulative deficits index in a representative sample of US adults.
    (Epidemiology and infection, 2018-06-14) Noppert, GA; Aiello, AE; O'Rand, AM; Cohen, HJ
    Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.
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    Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.
    (Mol Psychiatry, 2017-04-25) Duncan, LE; Ratanatharathorn, A; Aiello, AE; Almli, LM; Amstadter, AB; Ashley-Koch, AE; Baker, DG; Beckham, JC; Bierut, LJ; Bisson, J; Bradley, B; Chen, C-Y; Dalvie, S; Farrer, LA; Galea, S; Garrett, ME; Gelernter, JE; Guffanti, G; Hauser, MA; Johnson, EO; Kessler, RC; Kimbrel, NA; King, A; Koen, N; Kranzler, HR; Logue, MW; Maihofer, AX; Martin, AR; Miller, MW; Morey, RA; Nugent, NR; Rice, JP; Ripke, S; Roberts, AL; Saccone, NL; Smoller, JW; Stein, DJ; Stein, MB; Sumner, JA; Uddin, M; Ursano, RJ; Wildman, DE; Yehuda, R; Zhao, H; Daly, MJ; Liberzon, I; Ressler, KJ; Nievergelt, CM; Koenen, KC
    The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h(2)SNP) for European-American females of 29% that is similar to h(2)SNP for schizophrenia and is substantially higher than h(2)SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.77.