Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Modeling the Potential Impact of Missing Race and Ethnicity Data in Infectious Disease Surveillance Systems on Disparity Measures: Scenario Analysis of Different Imputation Strategies

BackgroundMonitoring progress toward population health equity goals requires developing robust disparity indicators. However, surveillance data gaps that result in undercounting racial and ethnic minority groups might influence the observed disparity measures. ObjectiveThis study aimed to assess the impact of missing race and ethnicity data in surveillance systems on disparity measures. MethodsWe explored variations in missing race and ethnicity information in reported annual chlamydia and gonorrhea diagnoses in the United States from 2007 to 2018 by state, year, reported sex, and infection. For diagnoses with incomplete demographic information in 2018, we estimated disparity measures (relative rate ratio and rate difference) with 5 imputation scenarios compared with the base case (no adjustments). The 5 scenarios used the racial and ethnic distribution of chlamydia or gonorrhea diagnoses in the same state, chlamydia or gonorrhea diagnoses in neighboring states, chlamydia or gonorrhea diagnoses within the geographic region, HIV diagnoses, and syphilis diagnoses. ResultsIn 2018, a total of 31.93% (560,551/1,755,510) of chlamydia and 22.11% (128,790/582,475) of gonorrhea diagnoses had missing race and ethnicity information. Missingness differed by infection type but not by reported sex. Missing race and ethnicity information varied widely across states and times (range across state-years: from 0.0% to 96.2%). The rate ratio remained similar in the imputation scenarios, although the rate difference differed nationally and in some states. ConclusionsWe found that missing race and ethnicity information affects measured disparities, which is important to consider when interpreting disparity metrics. Addressing missing information in surveillance systems requires system-level solutions, such as collecting more complete laboratory data, improving the linkage of data systems, and designing more efficient data collection procedures. As a short-term solution, local public health agencies can adapt these imputation scenarios to their aggregate data to adjust surveillance data for use in population indicators of health equity

Syphilis among adult males with a history of male-to-male sexual contact living with diagnosed HIV in New York State (excluding New York City): The challenge of intersecting epidemics.

Since 2009, syphilis has been increasing in New York State (NYS) excluding New York City (NYC) among men with a history of male-to-male sexual contact (MSM). Because MSM make up a disproportionate number of new HIV infections, this study aims to: 1) establish yearly rates of early syphilis diagnosis, 2) assess factors associated with early syphilis diagnosis, and 3) describe missed opportunities for earlier diagnosis of syphilis among MSM living with diagnosed HIV(MSMLWDH) in NYS, excluding NYC. A cohort of adult MSMLWDH alive in 2013 were followed through 2016 to identify individuals with at least one early syphilis diagnosis between July 2014 and December 2016. Early syphilis diagnosis rates were calculated for 2015 and 2016. Crude relative risks and 95% confidence intervals were calculated to determine associations between available covariates and both syphilis diagnosis and missed opportunities. Missed opportunities were defined as reports of an HIV-related laboratory test within a given window corresponding to syphilis staging where syphilis testing was not performed at the same time. Of 7,512 MSMLWDH, 50.0% were non-Hispanic white, 85.4% aged ≥35, and 320(4.3%) had an early syphilis diagnosis. Yearly rates were: 1,838/100,000, and 1,681/100,000 in 2015 and 2016, respectively. Persons who were non-Hispanic black, living with diagnosed HIV for less than three years, aged <45, and were always virally suppressed or always in HIV care were significantly more likely to have a syphilis diagnosis. Over half of individuals had evidence of a missed opportunity for earlier syphilis diagnosis. Syphilis stage at diagnosis, older age, and syphilis diagnosis not concurrent with an HIV-related laboratory test were associated with a higher likelihood of having a missed opportunity. This study supports high interrelatedness of the syphilis and HIV epidemics among MSM. Since syphilis can impact HIV viral load suppression status, efforts to end the HIV epidemic need to be coupled with syphilis elimination efforts

Factors associated with SARS-CoV-2-related hospital outcomes among and between persons living with and without diagnosed HIV infection in New York State.

BackgroundPersons living with diagnosed HIV (PLWDH) are at increased risk for severe illness due to COVID-19. The degree to which this due to HIV infection, comorbidities, or other factors remains unclear.MethodsWe conducted a retrospective matched cohort study of individuals hospitalized with COVID-19 in New York State between March and June 2020, during the first wave of the pandemic, to compare outcomes among 853 PLWDH and 1,621 persons without diagnosed HIV (controls). We reviewed medical records to compare sociodemographic and clinical characteristics at admission, comorbidities, and clinical outcomes between PLWDH and controls. HIV-related characteristics were evaluated among PLWDH.ResultsPLWDH were significantly more likely to have cardiovascular (matched prevalence-ratio [mPR], 1.22 [95% CI, 1.07-1.40]), chronic liver (mPR, 6.71 [95% CI, 4.75-9.48]), chronic lung (mPR, 1.76 [95% CI, 1.40-2.21]), and renal diseases (mPR, 1.77 [95% CI, 1.50-2.09]). PLWDH were less likely to have elevated inflammatory markers upon hospitalization. Relative to controls, PLWDH were 15% less likely to require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and 15% less likely to require admission to the intensive care unit. No significant differences were found in in-hospital mortality. PLWDH on tenofovir-containing regimens were significantly less likely to require mechanical ventilation or ECMO (risk-ratio [RR], 0.73 [95% CI, 0.55-0.96]) and to die (RR, 0.74 [95% CI, 0.57-0.96]) than PLWDH on non-tenofovir-containing regimens.ConclusionsWhile hospitalized PLWDH and controls had similar likelihood of in-hospital death, chronic disease profiles and degree of inflammation upon hospitalization differed. This may signal different mechanisms leading to severe COVID-19