Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults

Patel, Kushang V.

doi:10.3324/haematol.13692

Cited by 36 publications

(26 citation statements)

References 20 publications

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“…Our observations that men had higher Hb concentrations than women and that older adults had lower Hb levels and platelet counts than younger patients were in line with other studies 20, 21. Furthermore, Hb levels and platelet counts have been found to vary substantially according to age, gender, and race/ethnicity 20, 21.…”

Section: Discussionsupporting

confidence: 92%

Gender-Specific Prognosis and Risk Impact of C-Reactive Protein, Hemoglobin and Platelet in the Development of Coronary Spasm

Hung

Hsu

et al. 2013

Int. J. Med. Sci.

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Background: Scarce data are available on hemoglobin and platelet in relation to coronary artery spasm (CAS) development. We sought to determine the roles that high-sensitivity C-reactive protein (hs-CRP), hemoglobin and platelet play in CAS patients.Methods: Patients (337 women and 532 men) undergoing coronary angiography with or without CAS but without obstructive coronary artery disease were evaluated during a 12-year period.Results: Among women with high hemoglobin levels, the odds ratios (OR) from the lowest (<1 mg/l) to the highest tertiles (>3 mg/l) of hs-CRP were 1.21, 2.15, and 5.93 (p=0.009). In women with low hemoglobin levels, an elevated risk was found from the middle to the highest tertiles of hs-CRP (OR 0.59 to 3.85) (p=0.004). This relationship was not observed in men. In men, platelet count was the most significant risk factor for CAS (p=0.004). The highest likelihood of developing CAS was found among women with the highest hs-CRP tertile and low platelet counts (OR 8.77; 95% confidence interval [CI] 2.20-35.01) and among men with the highest hs-CRP tertile and high platelet counts (OR 4.58; 95% CI 0.48-43.97). Neither hemoglobin level nor platelet count was associated with frequent recurrent angina in both genders with CAS whereas death and myocardial infarction were rare.Conclusions: There are positive interactions among hs-CRP, hemoglobin and platelet in women with this disease, but not in men. While hemoglobin is a modifier in CAS development in women, platelet count is an independent risk factor for men. Both women and men have good prognosis of CAS.

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Section: Discussionsupporting

confidence: 92%

Gender-Specific Prognosis and Risk Impact of C-Reactive Protein, Hemoglobin and Platelet in the Development of Coronary Spasm

Hung

Hsu

et al. 2013

Int. J. Med. Sci.

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“…The statistical analysis was designed to account for these potential biases, as far as the data allowed. Inclusion of participants of different age groups further augments variability in terms of resting metabolic rate (Peng et al, 2014), resting cerebral blood flow (Lu et al, 2011), vascular CO 2 reactivity (Lu et al, 2011; Murphy et al, 2013); blood pressure (AlGhatrif et al, 2017); and hemoglobin concentration (Patel, 2008) all known to affect BOLD fMRI signal and/or the coupling of neural activity to the BOLD signal (D’Esposito et al, 1999; Levin et al, 2001; Patel et al, 2012; Murphy et al, 2013; Mark et al, 2015). Nevertheless, the uneven effect of aging on large-scale brain networks (e.g., DMN vs. MN), emphasized here and elsewhere (Song et al, 2014; Marstaller et al, 2015), probably indicates that age-related FC alterations cannot be merely attributed to changes in neurovascular coupling.…”

Section: Discussionmentioning

confidence: 99%

Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

Siman-Tov

Bosak

Sprecher

et al. 2017

Front. Aging Neurosci.

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As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life.

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“…RBC traits differ by self-reported ancestry, and both genetic (e.g., inherited hemoglobin variants) and acquired (e.g., iron deficiency, kidney disease) factors contribute to these ethnic differences[1, 2]. Quantitative RBC parameters are also polygenic traits that exhibit moderate to high heritability (trait-specific h 2 between 40% and 90%)[3–5]. Over 80 genomic regions have been associated with one or more RBC traits through genome-wide association studies (GWAS), performed primarily in European- and, to a lesser extent, Asian- and African-descent populations[6–14].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

et al. 2017

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Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos.

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Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults

Cited by 36 publications

References 20 publications

Gender-Specific Prognosis and Risk Impact of C-Reactive Protein, Hemoglobin and Platelet in the Development of Coronary Spasm

Gender-Specific Prognosis and Risk Impact of C-Reactive Protein, Hemoglobin and Platelet in the Development of Coronary Spasm

Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

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