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294 records · Page 17

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities ( h 2 ) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. Methods Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (β FS , h 2 ={(1 + 8r spouse β FS ) 0.5 - 1}/(2r spouse )) and offspring-parent regression slopes (β OP , h 2 = 2β OP /(1 + r spouse )) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. Results Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from β OP ( P trend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from β FS ( P trend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. Conclusion Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF- α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

59 BASIC BIOLOGICAL SCIENCES↗

Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution

Background: “Quantile-dependent expressivity” refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and the FEV 1 /FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability (h 2 ) is constant over all quantiles of their distribution. Methods: Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (β OP ), offspring-midparent (β OM ), and full-sib regression slopes (β FS ). Nonparametric significance levels were obtained from 1,000 bootstrap samples. β OP s were used as simple indicators of quantile-specific heritability (i.e.,h 2 = 2β OP /(1+r spouse ), where r spouse was the correlation between spouses). Results: β OP ± standard error (SE) decreased by 0.0009 ± 0.0003 (P = 0.003) with every one-percent increment in the population distribution of FEV 1 /FVC, i.e., β OP ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV 1 /FVC distribution, respectively. These correspond to h 2 ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV 1 /FVC ratio. Maximum mid-expiratory flow (MMEF) h 2 ± SEs increased 0.0025 ± 0.0007 (P = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific h 2 increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific h 2 , i.e., greater heritability in individuals with lower FEV 1 /FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals. Conclusion: Heritabilities of FEV 1 /FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.

59 BASIC BIOLOGICAL SCIENCES↗

The influence of incubation temperature on offspring traits varies across northern and southern populations of the American alligator ( Alligator mississippiensis )

Maternal provisioning and the developmental environment are fundamental determinants of offspring traits, particularly in oviparous species. However, the extent to which embryonic responses to these factors differ across populations to drive phenotypic variation is not well understood. Here, we examine the contributions of maternal provisioning and incubation temperature to hatchling morphological and metabolic traits across four populations of the American alligator (Alligator mississippiensis), encompassing a large portion of the species' latitudinal range. Our results show that whereas the influence of egg mass is generally consistent across populations, responses to incubation temperature show population-level variation in several traits, including mass, head length, head width, and residual yolk mass. Additionally, the influence of incubation temperature on developmental rate is greater at northern populations, while the allocation of maternal resources toward fat body mass is greater at southern populations. Overall, our results suggest that responses to incubation temperature, relative to maternal provisioning, are a larger source of interpopulation phenotypic variation and may contribute to the local adaptation of populations.

59 BASIC BIOLOGICAL SCIENCES↗

Adaptive changes in sexual behavior in the high–risk population in response to human monkeypox transmission in Canada can help control the outbreak: Insights from a two–group, two–route epidemic model

Monkeypox, a zoonotic disease, is emerging as a potential sexually transmitted infection/disease, with underlying transmission mechanisms still unclear. We devised a risk-structured, compartmental model, incorporating sexual behavior dynamics. We compared different strategies targeting the high-risk population: a scenario of control policies geared toward the use of condoms and/or sexual abstinence (robust control strategy) with risk compensation behavior change, and a scenario of control strategies with behavior change in response to the doubling rate (adaptive control strategy). Monkeypox's basic reproduction number is 1.464, 0.0066, and 1.461 in the high-risk, low-risk, and total populations, respectively, with the high-risk group being the major driver of monkeypox spread. Policies imposing condom use or sexual abstinence need to achieve a 35% minimum compliance rate to stop further transmission, while a combination of both can curb the spread with 10% compliance to abstinence and 25% to condom use. With risk compensation, the only option is to impose sexual abstinence by at least 35%. Adaptive control is more effective than robust control where the daily sexual contact number is reduced proportionally and remains constant thereafter, shortening the time to epidemic peak, lowering its size, facilitating disease attenuation, and playing a key role in controlling the current outbreak.

60 APPLIED LIFE SCIENCES↗

Physiological potential and evolutionary trajectories of syntrophic sulfate-reducing bacterial partners of anaerobic methanotrophic archaea

Sulfate-coupled anaerobic oxidation of methane (AOM) is performed by multicellular consortia of anaerobic methanotrophic archaea (ANME) in obligate syntrophic partnership with sulfate-reducing bacteria (SRB). Diverse ANME and SRB clades co-associate but the physiological basis for their adaptation and diversification is not well understood. In this work, we used comparative metagenomics and phylogenetics to investigate the metabolic adaptation among the 4 main syntrophic SRB clades (HotSeep-1, Seep-SRB2, Seep-SRB1a, and Seep-SRB1g) and identified features associated with their syntrophic lifestyle that distinguish them from their non-syntrophic evolutionary neighbors in the phylum Desulfobacterota. We show that the protein complexes involved in direct interspecies electron transfer (DIET) from ANME to the SRB outer membrane are conserved between the syntrophic lineages. In contrast, the proteins involved in electron transfer within the SRB inner membrane differ between clades, indicative of convergent evolution in the adaptation to a syntrophic lifestyle. Our analysis suggests that in most cases, this adaptation likely occurred after the acquisition of the DIET complexes in an ancestral clade and involve horizontal gene transfers within pathways for electron transfer (CbcBA) and biofilm formation (Pel). We also provide evidence for unique adaptations within syntrophic SRB clades, which vary depending on the archaeal partner. Among the most widespread syntrophic SRB, Seep-SRB1a, subclades that specifically partner ANME-2a are missing the cobalamin synthesis pathway, suggestive of nutritional dependency on its partner, while closely related Seep-SRB1a partners of ANME-2c lack nutritional auxotrophies. Our work provides insight into the features associated with DIET-based syntrophy and the adaptation of SRB towards it.

59 BASIC BIOLOGICAL SCIENCES↗