Gantman, Ana P., Sayeed Devraj-Kizuk, Peter Mende-Siedlecki, Jay J. Van Bavel, and Kyle E. Mathewson. 2019. “The Time-course of Moral Perception: An Electroencephalography Investigation.” PsyArXiv. August 26. doi:10.31234/osf.io/72dxa
Abstract: Humans are highly attuned to perceptual cues about their values. A growing body of evidence suggests that people selectively attend to moral stimuli. However, it is unknown whether morality is prioritized early in perception or much later in cognitive processing. We use a combination of behavioral methods and electroencephalography to investigate how early in perception moral words are prioritized relative to non-moral words. The behavioral data replicate previous research indicating that people are more likely to correctly identify moral than non-moral words in a modified lexical decision task. The electroencephalography data reveal that words are distinguished from non-words as early as 200 milliseconds after onset over frontal brain areas, and moral words are distinguished from non-moral words 100 milliseconds later over left-posterior cortex. Further analyses reveal that differences in brain activity to moral vs. non-moral words cannot be explained by differences in arousal associated with the words. These results suggest that moral content might be prioritized in conscious awareness after an initial perceptual encoding but before subsequent memory processing or action preparation. This work offers a more precise theoretical framework for understanding how morality impacts vision and behavior.
Monday, August 26, 2019
Gender Differences in Life Satisfaction Among Children and Adolescents: almost no differences
Gender Differences in Life Satisfaction Among Children and Adolescents: A Meta-analysis. Xinjie Chen et al. Journal of Happiness Studies, August 26 2019. https://link.springer.com/article/10.1007/s10902-019-00169-9
Abstract: Gender differences in life satisfaction (LS) have been studied for a long time, and the first meta-analysis on this issue was conducted almost 40 years ago. Since then, the social status of females has changed considerably across different nations and cultures. The individual studies in this area continued to show inconsistent results concerning gender group differences in their respective perception of LS. In this study, 46 empirical studies from 1980 to 2017 (with a cumulated total N = 11,772) were meta-analyzed to examine potential gender differences in LS among children and adolescents, and to explore if some study features could be moderators that could account for the observed inconsistencies in the findings across studies. The findings revealed that LS remains invariant across gender groups, but with a slight difference in favor of male children and adolescents. Our results further suggested that four study features were shown to contribute to the variations of the reported gender difference in LS across individual studies: geographical region, population type, age, and domain specific LS measurements. Such different features across the individual studies could have led to the observed inconsistency of the findings. Understanding how gender differences in LS vary by these study features could allow us to consider more targeted support to increase LS of children and adolescents in different situations.
Keywords: Life satisfaction Cognitive well-being Children and adolescents Gender difference Meta-analysis
Abstract: Gender differences in life satisfaction (LS) have been studied for a long time, and the first meta-analysis on this issue was conducted almost 40 years ago. Since then, the social status of females has changed considerably across different nations and cultures. The individual studies in this area continued to show inconsistent results concerning gender group differences in their respective perception of LS. In this study, 46 empirical studies from 1980 to 2017 (with a cumulated total N = 11,772) were meta-analyzed to examine potential gender differences in LS among children and adolescents, and to explore if some study features could be moderators that could account for the observed inconsistencies in the findings across studies. The findings revealed that LS remains invariant across gender groups, but with a slight difference in favor of male children and adolescents. Our results further suggested that four study features were shown to contribute to the variations of the reported gender difference in LS across individual studies: geographical region, population type, age, and domain specific LS measurements. Such different features across the individual studies could have led to the observed inconsistency of the findings. Understanding how gender differences in LS vary by these study features could allow us to consider more targeted support to increase LS of children and adolescents in different situations.
Keywords: Life satisfaction Cognitive well-being Children and adolescents Gender difference Meta-analysis
Morningness–Eveningness and Sociosexuality from a Life History Perspective
Chapter 4: Morningness–Eveningness and Sociosexuality from a Life History Perspective. James Marvel-Coen, Coltan Scrivner & Dario Maestripieri. In: The SAGE Handbook of Personality and Individual Differences: Volume II: Origins of Personality and Individual Differences. Edited by: Virgil Zeigler-Hill & Todd K. Shackelford. May 2018. http://dx.doi.org/10.4135/9781526451200.n4
Basic Aspects of Morningness.Eveningness
Many human biological processes are regulated by circadian rhythms, sometimes referred to as "internal clocks". These circadian rhythms apply to hormone concentrations, brain activity, heart rate, and body temperature. In humans and many other animals, a "master clock" is attuned to a 24-hour cycle, and corresponds to sleep and wakefulness. The master clock in humans operates through the action of the suprachiasmatic nucleus (SCN) in the hypothalamus (Herzog et al., 1998). Although our circadian rhythms have been selected for based on a general pattern of light and dark, environmental factors can influence circadian rhythms, and rhythms can vary between people.
Morningness-eveningness -or chronotype- refers to the notion that individuals vary from one another in preferences for the timing of waking up and falling asleep, as well as for diurnal peaks in activity and performance, such that some individuals tend to be more active, both cognitively and physiologically, in the morning, whereas others tend to be more active in the evening (Randler et al., 2016). Variation in morningness-eveningness tends to occur along a continuum, and the individuals at the two extremes of this continuum are often denoted as morning-types and evening-types, or "early birds" and "night owls". Research has shown that approximately 40% of individuals are either morning- or evening-types, with the other 60% falling into a more neutral category (Adan et al., 2012). Propensities for being a morning- or an evening-type are significantly heritable (e.g., Hur, 2007; Hur et al., 1998; Vink et al., 2001) but age, sex, and environment are important as well.
Children are typically morning-oriented but evening orientation tends to increase in both males and females throughout adolescence (Randler, 2011; Roenneberg et al., 2004). Sex differences in morningness-eveninness also begin to appear in adolescence, with more males being represented in the evening type category than females (Randler, 2007). However, these sex differences disappear after women reach menopause, suggesting that that they may be functionally linked to reproduction and be regulated by reproductive physiology, at least in women (Adan et al., 2012). Early experience and environment can influence variation in morningness-eveningness. For example, individuals who spend their first few months of life in a short photoperiod (i.e., autumn and winter) tend to be morning-types, whereas those who spend their first few months in a long photoperiod (i.e., spring and summer) tend to be evening-types (Mongrain et al., 2006; Natale and Di Milia, 2011). Latitude has also been shown to have a strong effect on chronotype, with people at northern latitudes having significantly later midpoints of sleep (Natale et al., 2009). This effect is moderated by residency type, however, with larger towns being less affected by latitude (Borisenkov et al., 2012). Thus, it is probable that sunlight, and potentially artificial light as well, plays a role in the development and shaping of chronotype. However, this effect is not entirely clear, as evening-types tend to have been exposed to more sunlight post-birth, but less during life.
Basic Aspects of Morningness.Eveningness
Many human biological processes are regulated by circadian rhythms, sometimes referred to as "internal clocks". These circadian rhythms apply to hormone concentrations, brain activity, heart rate, and body temperature. In humans and many other animals, a "master clock" is attuned to a 24-hour cycle, and corresponds to sleep and wakefulness. The master clock in humans operates through the action of the suprachiasmatic nucleus (SCN) in the hypothalamus (Herzog et al., 1998). Although our circadian rhythms have been selected for based on a general pattern of light and dark, environmental factors can influence circadian rhythms, and rhythms can vary between people.
Morningness-eveningness -or chronotype- refers to the notion that individuals vary from one another in preferences for the timing of waking up and falling asleep, as well as for diurnal peaks in activity and performance, such that some individuals tend to be more active, both cognitively and physiologically, in the morning, whereas others tend to be more active in the evening (Randler et al., 2016). Variation in morningness-eveningness tends to occur along a continuum, and the individuals at the two extremes of this continuum are often denoted as morning-types and evening-types, or "early birds" and "night owls". Research has shown that approximately 40% of individuals are either morning- or evening-types, with the other 60% falling into a more neutral category (Adan et al., 2012). Propensities for being a morning- or an evening-type are significantly heritable (e.g., Hur, 2007; Hur et al., 1998; Vink et al., 2001) but age, sex, and environment are important as well.
Children are typically morning-oriented but evening orientation tends to increase in both males and females throughout adolescence (Randler, 2011; Roenneberg et al., 2004). Sex differences in morningness-eveninness also begin to appear in adolescence, with more males being represented in the evening type category than females (Randler, 2007). However, these sex differences disappear after women reach menopause, suggesting that that they may be functionally linked to reproduction and be regulated by reproductive physiology, at least in women (Adan et al., 2012). Early experience and environment can influence variation in morningness-eveningness. For example, individuals who spend their first few months of life in a short photoperiod (i.e., autumn and winter) tend to be morning-types, whereas those who spend their first few months in a long photoperiod (i.e., spring and summer) tend to be evening-types (Mongrain et al., 2006; Natale and Di Milia, 2011). Latitude has also been shown to have a strong effect on chronotype, with people at northern latitudes having significantly later midpoints of sleep (Natale et al., 2009). This effect is moderated by residency type, however, with larger towns being less affected by latitude (Borisenkov et al., 2012). Thus, it is probable that sunlight, and potentially artificial light as well, plays a role in the development and shaping of chronotype. However, this effect is not entirely clear, as evening-types tend to have been exposed to more sunlight post-birth, but less during life.
Associations of dairy product consumption with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Italy cohort
Associations of dairy product consumption with mortality in the European
Prospective Investigation into Cancer and Nutrition (EPIC)–Italy
cohort. Valeria Pala et al. The American Journal of Clinical Nutrition,
nqz183, August 21 2019, https://doi.org/10.1093/ajcn/nqz183
ABSTRACT
Background:The relation of dairy product consumption to health and mortality is controversial.
Objectives: We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)–Italy study.
Methods: Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression.
Results: After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole.
Conclusions: In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose–response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality.
Keywords: dairy product consumption, mortality, EPIC-Italy, cancer, cardiovascular disease
ABSTRACT
Background:The relation of dairy product consumption to health and mortality is controversial.
Objectives: We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)–Italy study.
Methods: Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression.
Results: After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole.
Conclusions: In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose–response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality.
Keywords: dairy product consumption, mortality, EPIC-Italy, cancer, cardiovascular disease
Cato review: That 'Vaping-Linked Lung Disease' Might Not Really Be Linked to Vaping
That 'Vaping-Linked Lung Disease' Might Not Really Be Linked to Vaping. Elizabeth Nolan Brown. Cato Roundup, Aug 23 2019. https://reason.com/2019/08/23/that-vaping-linked-lung-disease-might-not-really-be-linked-to-vaping/
There's a bit of panic brewing in the press over lung problems that could be linked to vape products. The Centers for Disease Control and Prevention (CDC) "reports more than 150 cases of possible vaping-linked lung disease," says The Hill. Others make even bolder claims.
"More than 100 vapers have contracted a severe lung disease," The Verge reports. "Vaping lung disease: CDC reports 153 cases," says USA Today. Ars Technica warns that "vaping-linked lung disease cases" have jumped "from 94 to 153 in 5 days."
But read closely, and it becomes apparent that nobody actually knows if vaping is causing this mystery disease or not. Nobody even knows if there is a disease, or how many people actually have it. That's what the CDC is at the beginning of investigating.
For now, all officials know is that states keep reporting people with cases of mysterious lung and chest problems. "Many states have alerted CDC to possible (not confirmed) cases and investigations into these cases are ongoing," says the CDC. Symptoms include shortness of breath, chest pain, and coughing—all common issues that can stem from a range of causes and ailments.
"The CDC and impacted states haven't identified a cause," notes The Verge. Nor has it actually verified suspected cases.
Those reporting the problems all say they have used vape products—albeit not what sort. Which leaves us with another possibility: that some particular faulty product or line of products is indeed causing trouble, but that this is not an issue with vaping at large.
We know that some patients in potential cases used THC-containing vape products, not nicotine-containing e-cigarettes. The Vapor Technology Association told The Hill that no nicotine e-cigarettes have been linked to the lung issues:
The fact that cases have spiked dramatically in the brief time since news of this "vaping lung disease" started spreading suggests we may have a different sort of contagion on our hands. Perhaps people who vape have been starting to freak out upon hearing the "lung disease" news and either suddenly noticed new symptoms (which also sound a lot like symptoms of a panic attack) or began interpreting ongoing symptoms in a new way.
Or maybe vaping is going to kill us! That's certainly possible. The point is that right now, anything is possible. And until we know more, it's irresponsible for folks to spread panic about products that have been helping many people leave more dangerous habits behind.
There's a bit of panic brewing in the press over lung problems that could be linked to vape products. The Centers for Disease Control and Prevention (CDC) "reports more than 150 cases of possible vaping-linked lung disease," says The Hill. Others make even bolder claims.
"More than 100 vapers have contracted a severe lung disease," The Verge reports. "Vaping lung disease: CDC reports 153 cases," says USA Today. Ars Technica warns that "vaping-linked lung disease cases" have jumped "from 94 to 153 in 5 days."
But read closely, and it becomes apparent that nobody actually knows if vaping is causing this mystery disease or not. Nobody even knows if there is a disease, or how many people actually have it. That's what the CDC is at the beginning of investigating.
For now, all officials know is that states keep reporting people with cases of mysterious lung and chest problems. "Many states have alerted CDC to possible (not confirmed) cases and investigations into these cases are ongoing," says the CDC. Symptoms include shortness of breath, chest pain, and coughing—all common issues that can stem from a range of causes and ailments.
"The CDC and impacted states haven't identified a cause," notes The Verge. Nor has it actually verified suspected cases.
Those reporting the problems all say they have used vape products—albeit not what sort. Which leaves us with another possibility: that some particular faulty product or line of products is indeed causing trouble, but that this is not an issue with vaping at large.
We know that some patients in potential cases used THC-containing vape products, not nicotine-containing e-cigarettes. The Vapor Technology Association told The Hill that no nicotine e-cigarettes have been linked to the lung issues:
The e-cigarette makers' trade group called for public health officials to "refrain from assigning unsubstantiated blame until the facts are known," and said traditional nicotine-containing e-cigarettes are being wrongly conflated with THC-containing products.In actuality, we don't know at all what folks with many of the suspected cases were smoking, nor what other habits they may have shared, such as any history of regular cigarette or marijuana smoking. We don't—and this is pretty damn crucial—even know if all of these patients suffer from the same affliction at all.
The fact that cases have spiked dramatically in the brief time since news of this "vaping lung disease" started spreading suggests we may have a different sort of contagion on our hands. Perhaps people who vape have been starting to freak out upon hearing the "lung disease" news and either suddenly noticed new symptoms (which also sound a lot like symptoms of a panic attack) or began interpreting ongoing symptoms in a new way.
Or maybe vaping is going to kill us! That's certainly possible. The point is that right now, anything is possible. And until we know more, it's irresponsible for folks to spread panic about products that have been helping many people leave more dangerous habits behind.
"Eating with familiar others has a powerful effect of increasing food intakes." Except when women eat in the company of men.
A systematic review and meta-analysis of the social facilitation of eating. Helen K Ruddock, Jeffrey M Brunstrom, Lenny R Vartanian, Suzanne Higgs. The American Journal of Clinical Nutrition, nqz155, August 21 2019, https://doi.org/10.1093/ajcn/nqz155
ABSTRACT
Background: Research suggests that people tend to eat more when eating with other people, compared with when they eat alone, and this is known as the social facilitation of eating. However, little is known about when and why this phenomenon occurs.
Objectives: This review aimed to quantify the evidence for social facilitation of eating and identify moderating factors and underlying mechanisms.
Methods: We systematically reviewed studies that used experimental and nonexperimental approaches to examine food intake/food choice as a function of the number of co-eaters. The following databases were searched during April 2019: PsychInfo, Embase, Medline, and Social Sciences Citation Index. Studies that used naturalistic techniques were narratively synthesized, and meta-analyses were conducted to synthesize results from experimental studies.
Results: We reviewed 42 studies. We found strong evidence that people select and eat more when eating with friends, compared with when they eat alone [Z = 5.32; P < 0.001; standardized mean difference (SMD) = 0.76; 95% CI: 0.48, 1.03]. The meta-analysis revealed no evidence for social facilitation across studies that had examined food intake when participants ate alone or with strangers/acquaintances (Z = 1.32; P = 0.19; SMD = 0.21, 95% CI: −0.10, 0.51). There was some evidence that the social facilitation of eating is moderated by gender, weight status, and food type. However, this evidence was limited by a lack of experimental research examining the moderating effect of these factors on the social facilitation of eating among friends. In 2 studies, there was evidence that the effect of the social context on eating may be partly mediated by longer meal durations and the perceived appropriateness of eating.
Conclusions: Findings suggest that eating with others increases food intake relative to eating alone, and this is moderated by the familiarity of co-eaters. The review identifies potential mechanisms for the social facilitation of eating and highlights the need for further research to establish mediating factors. Finally, we propose a new theoretical framework in which we suggest that the social facilitation of eating has evolved as an efficient evolutionary adaptation.
Keywords: social facilitation, social influences, food intake, food choice, meta-analysis
ABSTRACT
Background: Research suggests that people tend to eat more when eating with other people, compared with when they eat alone, and this is known as the social facilitation of eating. However, little is known about when and why this phenomenon occurs.
Objectives: This review aimed to quantify the evidence for social facilitation of eating and identify moderating factors and underlying mechanisms.
Methods: We systematically reviewed studies that used experimental and nonexperimental approaches to examine food intake/food choice as a function of the number of co-eaters. The following databases were searched during April 2019: PsychInfo, Embase, Medline, and Social Sciences Citation Index. Studies that used naturalistic techniques were narratively synthesized, and meta-analyses were conducted to synthesize results from experimental studies.
Results: We reviewed 42 studies. We found strong evidence that people select and eat more when eating with friends, compared with when they eat alone [Z = 5.32; P < 0.001; standardized mean difference (SMD) = 0.76; 95% CI: 0.48, 1.03]. The meta-analysis revealed no evidence for social facilitation across studies that had examined food intake when participants ate alone or with strangers/acquaintances (Z = 1.32; P = 0.19; SMD = 0.21, 95% CI: −0.10, 0.51). There was some evidence that the social facilitation of eating is moderated by gender, weight status, and food type. However, this evidence was limited by a lack of experimental research examining the moderating effect of these factors on the social facilitation of eating among friends. In 2 studies, there was evidence that the effect of the social context on eating may be partly mediated by longer meal durations and the perceived appropriateness of eating.
Conclusions: Findings suggest that eating with others increases food intake relative to eating alone, and this is moderated by the familiarity of co-eaters. The review identifies potential mechanisms for the social facilitation of eating and highlights the need for further research to establish mediating factors. Finally, we propose a new theoretical framework in which we suggest that the social facilitation of eating has evolved as an efficient evolutionary adaptation.
Keywords: social facilitation, social influences, food intake, food choice, meta-analysis
Study of telomere length in older persons: Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls
Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants. Chia-Ling Kuo Luke C. Pilling George A. Kuchel Luigi Ferrucci David Melzer. Aging Cell, August 24 2019. https://doi.org/10.1111/acel.13017
Abstract: Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.
1 INTRODUCTION
Telomeres are end fragments of chromosomes consisting of thousands of repeats of the noncoding sequence TTAGGG. Telomeres function to protect chromosome ends against genomic instability. Telomeres shorten with each cell cycle and contribute to replicative senescence when reaching the Hayflick limit (Hayflick & Moorhead, 1961). Telomerase is a ribonucleoprotein complex, which replenishes telomere loss during replication. Telomerase is active at early developmental stages but almost completely inactive in somatic tissues of adults (Collins and Mitchell, 2002). Telomerase activation may treat aging‐related diseases and prolong human lifespan (de Jesus & Blasco, 2013). Previous studies on adult or old mice have shown successes from improving physical function and lifespan without increasing incidence of cancer, but the translation from mice to humans is unknown (de Jesus & Blasco, 2013).
Telomere length is often approximated using leukocyte telomere length, which is easy to extract from blood and highly correlated with telomere length in other tissues (Daniali et al., (2013)). Measured telomere length has been associated with mortality and aging‐related outcomes in humans (Mather, Jorm, Parslow, & Christensen 2011; Sanders & Newman, 2013; Brown, Zhang, Mitchel, & Ailshire, 2018), including cancer (Zhang et al., 2017), cardiovascular disease (Haycock et al., 2014), cognitive function, physical performance such as grip strength, sarcopenia, and frailty (Lorenzi et al., 2018; Zhou et al., 2018), plus biomarkers of lung function, blood pressure, bone mineral density, cholesterol, interleukin 6, and C‐reactive protein. Observational associations cannot be consistently replicated likely due to study populations, measurement methods, and statistical modelling (Sanders & Newman, 2013). In addition, a number of factors may confound observational associations such as sex and race/ethnicity, paternal age at birth, smoking, psychological stress, and other psychosocial, environmental, and behavioral factors (Blackburn, Epel, & Lin, 2015; Starkweather et al., 2014).
Telomere length has a strong inherited genetic component in humans (heritability estimates ranging from 34% to 82% (Broer, Codd, & Nyholt 2013). Mendelian randomization (MR) is a powerful statistical method to evaluate the causal relationship between an exposure and an outcome, under certain assumptions (Davey Smith & Hemani, 2014). Analogous to randomized clinical trials, MR creates groups determined by genotypes, which are inherited at random and are independent of confounding factors. In theory, if the groups are associated with the outcome, the association is independent of confounders and is via the exposure, assuming no pleiotropy is present. MR studies are more robust than observational studies to confounding effects, measurement errors or bias, and reverse causation (i.e., free of downstream effects appearing to be causes).
By applying MR, we were able to study the effect of telomere length on aging, with robustness to confounding effects. To date, 16 inherited genetic variants from genome‐wide association studies (GWAS) have been shown to be strongly associated with human leukocyte telomere length using European‐descent population samples (Haycock et al., 2017). Many of these loci harbor telomerase and telomere‐protective protein genes, including TERC, TERT, NAF1, OBFC1, and RTEL1 (Codd et al., 2013; Haycock et al., 2017). These variants have been used to perform MR, but the focus was on diseases (Haycock et al., 2017; Zhan et al., 2015). Additionally, previous studies tend to be underpowered due to an insufficiently large sample size for a small percent of variance (2%–3%) explained by the genetic variants (Haycock et al., 2017). The small percent of variance affects the power but not validity of the causal inference, if the genetic variants meet the Mendelian randomization assumptions: (a) associated with telomere length, (b) independent of all confounders for the association between telomere length and the outcome, and (c) independent of the outcome conditional on telomere length and all the confounders (Haycock et al., 2017).
In this study, we investigated causal relationships between telomere length and aging‐related outcomes with the focus on common measures of human aging such as grip strength, frailty, and cognitive function. We analyzed European‐descent participants from UK Biobank, with a wealth of genetic and phenotypic data. This study was not designed to analyze every aging trait in UK Biobank. Instead, we selected traits to cover different aspects of aging, using inputs from senior investigators in the team. Cancer, coronary heart disease, hypertension, and pneumonia were selected as they were common in older adults, but we did not attempt to include every individual disease. Disease‐specific MR associations were reported elsewhere (Haycock et al., 2017). Our project is focused on aging traits and is not powered for diseases that require a longer time to accumulate sufficient cases.
Abstract: Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.
1 INTRODUCTION
Telomeres are end fragments of chromosomes consisting of thousands of repeats of the noncoding sequence TTAGGG. Telomeres function to protect chromosome ends against genomic instability. Telomeres shorten with each cell cycle and contribute to replicative senescence when reaching the Hayflick limit (Hayflick & Moorhead, 1961). Telomerase is a ribonucleoprotein complex, which replenishes telomere loss during replication. Telomerase is active at early developmental stages but almost completely inactive in somatic tissues of adults (Collins and Mitchell, 2002). Telomerase activation may treat aging‐related diseases and prolong human lifespan (de Jesus & Blasco, 2013). Previous studies on adult or old mice have shown successes from improving physical function and lifespan without increasing incidence of cancer, but the translation from mice to humans is unknown (de Jesus & Blasco, 2013).
Telomere length is often approximated using leukocyte telomere length, which is easy to extract from blood and highly correlated with telomere length in other tissues (Daniali et al., (2013)). Measured telomere length has been associated with mortality and aging‐related outcomes in humans (Mather, Jorm, Parslow, & Christensen 2011; Sanders & Newman, 2013; Brown, Zhang, Mitchel, & Ailshire, 2018), including cancer (Zhang et al., 2017), cardiovascular disease (Haycock et al., 2014), cognitive function, physical performance such as grip strength, sarcopenia, and frailty (Lorenzi et al., 2018; Zhou et al., 2018), plus biomarkers of lung function, blood pressure, bone mineral density, cholesterol, interleukin 6, and C‐reactive protein. Observational associations cannot be consistently replicated likely due to study populations, measurement methods, and statistical modelling (Sanders & Newman, 2013). In addition, a number of factors may confound observational associations such as sex and race/ethnicity, paternal age at birth, smoking, psychological stress, and other psychosocial, environmental, and behavioral factors (Blackburn, Epel, & Lin, 2015; Starkweather et al., 2014).
Telomere length has a strong inherited genetic component in humans (heritability estimates ranging from 34% to 82% (Broer, Codd, & Nyholt 2013). Mendelian randomization (MR) is a powerful statistical method to evaluate the causal relationship between an exposure and an outcome, under certain assumptions (Davey Smith & Hemani, 2014). Analogous to randomized clinical trials, MR creates groups determined by genotypes, which are inherited at random and are independent of confounding factors. In theory, if the groups are associated with the outcome, the association is independent of confounders and is via the exposure, assuming no pleiotropy is present. MR studies are more robust than observational studies to confounding effects, measurement errors or bias, and reverse causation (i.e., free of downstream effects appearing to be causes).
By applying MR, we were able to study the effect of telomere length on aging, with robustness to confounding effects. To date, 16 inherited genetic variants from genome‐wide association studies (GWAS) have been shown to be strongly associated with human leukocyte telomere length using European‐descent population samples (Haycock et al., 2017). Many of these loci harbor telomerase and telomere‐protective protein genes, including TERC, TERT, NAF1, OBFC1, and RTEL1 (Codd et al., 2013; Haycock et al., 2017). These variants have been used to perform MR, but the focus was on diseases (Haycock et al., 2017; Zhan et al., 2015). Additionally, previous studies tend to be underpowered due to an insufficiently large sample size for a small percent of variance (2%–3%) explained by the genetic variants (Haycock et al., 2017). The small percent of variance affects the power but not validity of the causal inference, if the genetic variants meet the Mendelian randomization assumptions: (a) associated with telomere length, (b) independent of all confounders for the association between telomere length and the outcome, and (c) independent of the outcome conditional on telomere length and all the confounders (Haycock et al., 2017).
In this study, we investigated causal relationships between telomere length and aging‐related outcomes with the focus on common measures of human aging such as grip strength, frailty, and cognitive function. We analyzed European‐descent participants from UK Biobank, with a wealth of genetic and phenotypic data. This study was not designed to analyze every aging trait in UK Biobank. Instead, we selected traits to cover different aspects of aging, using inputs from senior investigators in the team. Cancer, coronary heart disease, hypertension, and pneumonia were selected as they were common in older adults, but we did not attempt to include every individual disease. Disease‐specific MR associations were reported elsewhere (Haycock et al., 2017). Our project is focused on aging traits and is not powered for diseases that require a longer time to accumulate sufficient cases.
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