scholarly journals The Long Life Family Study: Sequencing Exceptional Pedigrees for Rare Protective Variants

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 851-852
Author(s):  
Michael Province ◽  
Kaare Christensen ◽  
Stephanie Consentino ◽  
Joseph Lee ◽  
Anne Newman ◽  
...  

Abstract The Long Life Family Study (LLFS) has longitudinally measured key aging phenotypes on 4,953 participants (539 pedigrees) in the USA and Denmark selected for exceptional familial longevity. On average, both generations of the LLFS sample are healthier than average for their age/sex, for many phenotypes. However, the pedigrees are heterogeneous, with different families showing familial clustering of protection for different phenotypes. Linkage analyses identified extremely strong genetic linkage peaks for many cross-sectional as well as longitudinal trajectory rates of change phenotypes. These peaks are NOT explained by GWAS SNPs (either measured or imputed). Pedigree specific HLODs and preliminary deep sequencing suggests that these peaks are driven by rare, protective variants running in selected pedigrees. Whole Genome Sequencing, a third longitudinal visit, and extensive OMICs (transcriptomics, epigenomics, metabolomics and proteomics) will help us resolve the mechanisms behind these protective genetically linked variants, and could illuminate new biology and enable new therapeutics.

2021 ◽  
Vol 79 (1) ◽  
pp. 117-125
Author(s):  
Mengtian Du ◽  
Stacy L. Andersen ◽  
Nicole Schupf ◽  
Mary F. Feitosa ◽  
Megan S. Barker ◽  
...  

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods: We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (≤1935, or >1935), and the number of copies of ɛ2 or ɛ4 alleles. Results: Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE ɛ4 allele on Logical Memory. Participants carrying at least one copy of the ɛ4 allele had lower scores in both immediate (–0.31 points, 95% CI: –0.57, –0.05) and delayed (–0.37 points, 95% CI: –0.64, –0.10) recall comparing to non-ɛ4 allele carriers. We did not detect any significant longitudinal effect of the ɛ4 allele. There was no cross-sectional or longitudinal effect of the ɛ2 allele. Conclusion: The APOE ɛ4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE ɛ2 allele was not significantly associated with any of the cognitive test scores.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206873 ◽  
Author(s):  
Alexander M. Kulminski ◽  
Amisha V. Barochia ◽  
Yury Loika ◽  
Nalini Raghavachari ◽  
Konstantin G. Arbeev ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 501-501
Author(s):  
Nicole Roth ◽  
Paola Sebastiani ◽  
Stephanie Cosentino ◽  
Nicole Schupf ◽  
Thomas Perls ◽  
...  

Abstract Familial longevity and greater involvement in activities purported to build cognitive reserve (e.g. education, cognitively stimulating leisure activity) have both been associated with better cognitive function in later life, yet little is known about how these protective factors relate with one another. In this work, we modeled the associations among familial longevity, proxies of cognitive reserve, and cognitive function in the Long Life Family Study (LLFS). We assessed cognitive function using a comprehensive battery of neuropsychological tests (i.e. Digit-Spans, California Verbal Learning Test, Rey-Osterrieth Complex Figure, phonemic fluency, category fluency, Word Generation, DKEFS Sorting Test, and logical memory) in a subset of LLFS family members and a referent cohort (N=314, mean age 75.7±14.6 years). To model these associations, we used a series of Bayesian hierarchical regression pathways that incorporate a random effect for family relatedness, adjusted by age and sex. All continuous variables were rescaled and bounded to be approximately between (0,1) in order to standardize regression coefficients and to allow for an asymmetrical beta-distribution. Controlling for education level, age, and sex, referents had greater engagement in late-life cognitive activities compared to LLFS family members, β=0.38 (95% CI: 0.18 to 0.57). In turn, those with higher markers of cognitive reserve exhibited better neuropsychological performance. Despite LLFS family members having lower participation in cognitively stimulating leisure activities, there were no differences between LLFS family members and referents on cognitive test performance. These results suggest long-lived family members may have more unique pathways (i.e. genetic/environmental) that preserve cognition later in life.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert C. Kaplan ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
Martha L. Daviglus ◽  
...  

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043863
Author(s):  
Jingyuan Wang ◽  
Ke Tang ◽  
Kai Feng ◽  
Xin Lin ◽  
Weifeng Lv ◽  
...  

ObjectivesWe aim to assess the impact of temperature and relative humidity on the transmission of COVID-19 across communities after accounting for community-level factors such as demographics, socioeconomic status and human mobility status.DesignA retrospective cross-sectional regression analysis via the Fama-MacBeth procedure is adopted.SettingWe use the data for COVID-19 daily symptom-onset cases for 100 Chinese cities and COVID-19 daily confirmed cases for 1005 US counties.ParticipantsA total of 69 498 cases in China and 740 843 cases in the USA are used for calculating the effective reproductive numbers.Primary outcome measuresRegression analysis of the impact of temperature and relative humidity on the effective reproductive number (R value).ResultsStatistically significant negative correlations are found between temperature/relative humidity and the effective reproductive number (R value) in both China and the USA.ConclusionsHigher temperature and higher relative humidity potentially suppress the transmission of COVID-19. Specifically, an increase in temperature by 1°C is associated with a reduction in the R value of COVID-19 by 0.026 (95% CI (−0.0395 to −0.0125)) in China and by 0.020 (95% CI (−0.0311 to −0.0096)) in the USA; an increase in relative humidity by 1% is associated with a reduction in the R value by 0.0076 (95% CI (−0.0108 to −0.0045)) in China and by 0.0080 (95% CI (−0.0150 to −0.0010)) in the USA. Therefore, the potential impact of temperature/relative humidity on the effective reproductive number alone is not strong enough to stop the pandemic.


Neurosurgery ◽  
2021 ◽  
Author(s):  
Priyank Khandelwal ◽  
Fawaz Al-Mufti ◽  
Ambooj Tiwari ◽  
Amit Singla ◽  
Adam A Dmytriw ◽  
...  

Abstract BACKGROUND While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.


Author(s):  
Jessica Soldavini ◽  
Hazael Andrew ◽  
Maureen Berner

Abstract The prevalence of food insecurity in the USA has increased since the start of the COVID-19 pandemic; however, past studies have not examined how the food security status of college students has been impacted. The purpose of this study was to examine changes in the prevalence of food insecurity; determine the proportion of students experiencing a change in food security status; and identify characteristics associated with changes in food security status from before to during the COVID-19 pandemic among a sample of college students. We administered a cross-sectional online survey to students from a large public university in the Southeastern USA. The 10-item U.S. Adult Food Security Module was used to assess food security status during the spring 2020 semester both before and during the COVID-19 pandemic, and students self-reported a variety of individual characteristics. The overall prevalence of food insecurity increased by approximately one-third during the spring 2020 semester from before to during the COVID-19 pandemic. When examining the types of changes in food security status experienced by students, 12% improved, 68% stayed the same, and 20% worsened. A variety of characteristics were associated with an improvement or worsening of food security status category from before to during the pandemic. Similar to what is seen in other reports, we found that the overall proportion of college students in our sample experiencing food insecurity increased during the COVID-19 pandemic; however, some students showed improvements in food security status. Approaches for addressing food insecurity during and beyond the pandemic are needed.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044600
Author(s):  
Jessica Y. Islam ◽  
Denise C. Vidot ◽  
Marlene Camacho-Rivera

BackgroundPreventive behaviours have been recommended to control the spread of SARS-CoV-2. Adults with chronic diseases (CDs) are at higher risk of COVID-19-related mortality compared to the general population. Our objective was to evaluate adherence to COVID-19 preventive behaviours among adults without CDs compared with those with CDs and identify determinants of non-adherence to COVID-19 preventive behaviours.Study designCross-sectional.Setting and participantsWe used data from the nationally representative COVID-19 Impact Survey (n=10 760) conducted in the USA.Primary measuresAdults with CDs were categorised based on a self-reported diagnosis of diabetes, high blood pressure, heart disease/heart attack/stroke, asthma, chronic obstructive pulmonary disease (COPD), bronchitis or emphysema, cystic fibrosis, liver disease, compromised immune system, or cancer (54%).ResultsCompared with adults without CDs, adults with CDs were more likely to adhere to preventive behaviours including wearing a face mask (χ2-p<0.001), social distancing (χ2-p<0.001), washing or sanitising hands (χ2-p<0.001), and avoiding some or all restaurants (χ2-p=0.002) and public or crowded places (χ2-p=0.001). Adults with a high school degree or below [Adjusted prevalence ratio (aPR):1.82, 95% Confidence interval (CI)1.04 to 3.17], household income <US$50 000 (aPR:2.03, 95% CI 1.34 to 2.72), uninsured (aPR:1.65, 95% CI1.09 to 2.52), employed (aPR:1.48, 95% CI 1.02 to 2.17), residing in rural areas (aPR:1.70, 95% CI 1.01 to 2.85) and without any CD (aPR:1.78, 95% CI 1.24 to 2.55) were more likely to not adhere to COVID-19 preventive behaviours.ConclusionAdults with CDs are more likely to adhere to recommended COVID-19 preventive behaviours. Public health messaging targeting specific demographic groups and geographic areas, such as adults without CD or adults living in rural areas, should be prioritised.


2021 ◽  
Vol 3 (3) ◽  
pp. e148-e157 ◽  
Author(s):  
Benjamin Rader ◽  
Laura F White ◽  
Michael R Burns ◽  
Jack Chen ◽  
Joseph Brilliant ◽  
...  

2021 ◽  
Vol 6 (1) ◽  
pp. e000692
Author(s):  
Robert M Madayag ◽  
Erica Sercy ◽  
Gina M Berg ◽  
Kaysie L Banton ◽  
Matthew Carrick ◽  
...  

IntroductionThe COVID-19 pandemic has had major effects on hospitals’ ability to perform scientific research while providing patient care and minimizing virus exposure and spread. Many non-COVID-19 research has been halted, and funding has been diverted to COVID-19 research and away from other areas.MethodsA 28-question survey was administered to all level 1 trauma centers in the USA that included questions about how the pandemic affected the trauma centers’ ability to fulfill the volume and research requirements of level 1 verification by the American College of Surgeons (ACS).ResultsThe survey had a 29% response rate (40/137 successful invitations). Over half of respondents (52%) reported reduced trauma admissions during the pandemic, and 7% reported that their admissions dropped below the volume required for level 1 verification. Many centers diverted resources from research during the pandemic (44%), halted ongoing consenting studies (33%), and had difficulty fulfilling research requirements because of competing clinical priorities (40%).DiscussionResults of this study show a need for flexibility in the ACS verification process during the COVID-19 pandemic, potentially including reduction of the required admissions and/or research publication volumes.Level of evidenceLevel IV, cross-sectional study.


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