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BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

BACKGROUND: We examined over a million California birth records for 2010 through 2021 to investigate whether disparities in preterm birth (PTB) by nativity and race support the widely held but hitherto unsubstantiated belief that genetic differences explain the persistent Black-White disparity in PTB. METHODS: We examined PTB rates and risk ratios among African-, Caribbean-, and U.S.-born Black women compared to U.S.-born White women. Multivariate analyses adjusted for maternal age, education, number of live births, delivery payer, trimester of prenatal care initiation, pre-pregnancy BMI, smoking, and prevalence of poverty in a womans residence census tract; and for paternal education. RESULTS: In adjusted analyses, African-born Black womens PTB rates were no different from those of U.S.-born White women. DISCUSSION: The results add to prior evidence making a genetic etiology for the racial disparity in PTB unlikely. If genetic differences tied to race explained the Black-White disparity in PTB among U.S.-born women, the African immigrants in this study would have had higher rates of PTB, not the lower rates observed. Multiple explanations for the observed patterns and their implications are discussed. Failure to distinguish causes of PTB from causes of the racial disparity in PTB have likely contributed to erroneous attribution of the racial disparity to genetic differences. Based on the literature, unmeasured experiences of racism, including racism-related stress and adverse environmental exposures, are plausible explanations for the PTB disparity between Black and White U.S.-born women. The favorable birth outcomes of African-born Black immigrants may reflect less exposure to racism during sensitive life periods, e.g., childhood, when they were in African countries, where Black people are in the racial majority.

In 2017-2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparitys social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a womans microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.

In this Commentary, we argue that in line with the dramatic increase in the collection, storage, and curation of human genomic data for biomedical research, genomic data repositories and consortia have adopted governance frameworks to address the dual objectives of enabling wide access while protecting against possible harms. However, there are ongoing debates in the scientific community about the merits and limitations of different governance frameworks in achieving these twin aims; and indeed, best practices and points for consideration are notably absent when it comes to devising a governance framework for genomic databases. Based on our collective experience of devising and assessing governance frameworks, our Commentary identifies five key functions of “good governance” (or what makes “better governance”) and three areas where trade-offs should be considered when specifying policies within those functions. We apply these functions as a benchmark to describe, as an example, the governance frameworks of six large-scale international genomic projects.

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base.

The objectives of this study were to study maternal preferences for the return of their child’s genetic results and to describe the experiences, perceptions, attitudes and values that are brought to bear when individuals from different racial and cultural backgrounds consider participating in genetic research. We recruited women with diverse sociodemographic profiles to participate in seven focus groups. Twenty-eight percent of participants self-identified as Hispanic; 49% as White, Non-Hispanic; and 21% as Asian or Asian American. Focus groups were conducted in English or Spanish and were audio-recorded and transcribed verbatim. Transcripts were analyzed using qualitative thematic methods. Results indicated that preferences and decisions regarding the return of results may depend on both research and individual contextual factors. Participants understood the return of results as a complex issue, where individual and cultural differences in preferences are certain to arise. Another key finding was that participants desired an interpersonal, dynamic, flexible process that accommodated individual preferences and contextual differences for returning results. Our findings indicate a need to have well-developed systems for allowing participants to make and change over time their choices regarding the return of their child’s genetic results.

We examined the experiences, perceptions, and values that are brought to bear when individuals from different ethnic and cultural backgrounds consider participating in health research. Fifty-three women from Latino, Asian American, Middle Eastern, or Non-Latino, White backgrounds participated in seven English or Spanish focus groups facilitated by trained investigators using a standard protocol. Investigators described the National Children's Study (NCS) and then asked questions to elicit potential concerns, expectations, and informational needs. Group sessions were audio-recorded, transcribed verbatim, and analyzed using qualitative thematic methods. A major theme that emerged during focus groups was participant self-identification as a member of a cultural group or community when raising issues that would influence their decision to participate in research. A related theme was the belief by some that communities may differ in the ease of participation in the NCS. Identified themes related to the informed consent process included perceived risks, anticipated burden, perceived benefits, informational needs, and decision-making strategies. Although themes were shared across groups, there were cultural differences within themes. Findings indicated that individuals from diverse backgrounds may have different perspectives on and expectations for the research process. To effectively recruit representative samples, it will be important to address a range of issues relevant for informed consent and to consider the impact of participation on both individuals and communities.

OBJECTIVE:Women's health centers have been increasing in number but remain relatively unstudied. We examined patient expectations and quality of care at a hospital-based women's health center compared with those at a general medicine clinic. DESIGN:Cross-sectional survey. SETTING:University hospital-affiliated women's health and general internal medicine clinics. PARTICIPANTS:An age-stratified random sample of 2,000 women over 18 years of age with at least two visits to either clinic in the prior 24 months. We confined the analysis to 706 women respondents who identified themselves as primary care patients of either clinic. MEASUREMENTS AND MAIN RESULTS:Personal characteristics, health care utilization, preferences and expectations for care, receipt of preventive services, and satisfaction with provider and clinic were assessed for all respondents. Patients obtaining care at the general internal medicine clinic were older and had more chronic diseases and functional limitations than patients receiving care at the women's health center. Women's health center users (n = 357) were more likely than general medicine clinic users ( n = 349) to prefer a female provider ( 57% vs 32%, p =.0001) and to have sought care at the clinic because of its focus on women's health (49% vs 17%, p =. 0001). After adjusting for age and self-assessed health status, women's health center users were significantly more likely to report having had mammography (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.1, 15.2) and cholesterol screening (OR 1.6, 95% CI 1.0, 2.6) but significantly less likely to report having undergone flexible sigmoidoscopy (OR 0.5, 95% CI 0.3, 0.9). There were no significant differences between the clinics on receipt of counseling about hormone replacement therapy or receipt of Pap smear, or in satisfaction. CONCLUSIONS:These results suggest that, at least in this setting, women's health centers provide care to younger women and those with fewer chronic medical conditions and may meet a market demand. While the quality of gender-specific preventive care may be modestly better in women's health centers, the quality of general preventive care may be better in general medical clinics.