Survival to extreme ages clusters within families. However, identifying genetic loci conferring longevity and low morbidity in such longevous families is challenging. There is debate concerning the survival percentile that best isolates the genetic component in longevity. Here, we use three-generational mortality data from two large datasets, UPDB (US) and LINKS (Netherlands). We study 20,360 unselected families containing index persons, their parents, siblings, spouses, and children, comprising 314,819 individuals. Our analyses provide strong evidence that longevity is transmitted as a quantitative genetic trait among survivors up to the top 10% of their birth cohort. We subsequently show a survival advantage, mounting to 31%, for individuals with top 10% surviving first and second-degree relatives in both databases and across generations, even in the presence of non-longevous parents. To guide future genetic studies, we suggest to base case selection on top 10% survivors of their birth cohort with equally long-lived family members.
19 April 2021 in Proceedings of the National Academy of Sciences
Highly public anti-Black violence in the United States may cause widely experienced distress for Black Americans. This study identifies 49 publicized incidents of racial violence and quantifies national interest based on Google searches; incidents include police killings of Black individuals, decisions not to indict or convict the officer involved, and hate crime murders. Weekly time series of population mental health are produced for 2012 through 2017 using two sources: 1) Google Trends as national search volume for psychological distress terms and 2) the Behavioral Risk Factor Surveillance System (BRFSS) as average poor mental health days in the past 30 d among Black respondents (mean weekly sample size of 696). Autoregressive moving average (ARMA) models accounted for autocorrelation, monthly unemployment, season and year effects, 52-wk lags, news-related searches for suicide (for Google Trends), and depression prevalence and percent female (for BRFSS). National search interest varied more than 100-fold between racial violence incidents. Black BRFSS respondents reported 0.26 more poor mental health days during weeks with two or more racial incidents relative to none, and 0.13 more days with each log10 increase in national interest. Estimates were robust to sensitivity tests, including controlling for monthly number of Black homicide victims and weekly search interest in riots. As expected, racial incidents did not predict average poor mental health days among White BRFSS respondents. Results with national psychological distress from Google Trends were mixed but generally unsupportive of hypotheses. Reducing anti-Black violence may benefit Black Americans’ mental health nationally. Significance Violent acts that are widely publicized and perceived as anti-Black may harm the mental health of observers, particularly Black Americans. We identified 49 incidents of racial violence in the United States, occurring between 2013 and 2017 and receiving widely varying levels of search interest. We show that Black but not White Americans reported poorer mental health in weeks when two incidents of anti-Black violence occurred and when national interest was higher. Reducing racial violence, including police killings of Black individuals, is likely to benefit the mental health of Black Americans nationally.
12 October 2011 in Proceedings Of The Royal Society B-Biological Sciences
Women withBRCA1/2mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers ofBRCA1/2mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive forBRCA1/2mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly forBRCA1/2mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played byBRCA1/2mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.
Research into the genetic component of human longevity can provide important insights in mechanisms that may protect against age-related diseases and multi-morbidity. Thus far only a limited number of robust longevity loci have been detected in either candidate or genome wide association studies. One of the issues in these genetic studies is the definition of the trait being either lifespan, including any age at death or longevity, i.e. survival above a diverse series of thresholds. Likewise heritability and segregation research have conflated lifespan with longevity. The heritability of lifespan estimated across most studies has been rather low. Environmental factors have not been sufficiently investigated and the total amount of genetic variance contributing to longevity has not been estimated in sufficiently well-defined and powered studies. Up to now, genetic longevity studies lack the required insights into the nature and size of the genetic component and the optimal strategies for meta-analysis and subject selection for Next Generation Sequencing efforts. Historical demographic data containing deep genealogical information may help in estimating the best definition and heritability for longevity, its transmission patterns in multi-generational datasets and may allow relevant additive and modifying environmental factors such as socio-economic status, geographical background, exposure to environmental effects, birth order, and number of children to be included. In this light historical demographic data may be very useful for identifying lineages in human populations that are worth investigating further by geneticists.