Sweden: Intellectual disability was substantially heritable with 93pct–98pct of the variance in liability attributed to genetic influences

Familial risk and heritability of intellectual disability: a population-based cohort study in Sweden. Paul Lichtenstein et al. Journal of Child Psychology and Psychiatry, December 18 2021 https://doi.org/10.1111/jcpp.13560

Abstract

Background: Intellectual disability (ID) aggregates in families, but factors affecting individual risk and heritability estimates remain unknown.

Methods: A population-based family cohort study of 4,165,785 individuals born 1973–2013 in Sweden, including 37,787 ID individuals and their relatives. The relative risks (RR) of ID with 95% confidence intervals (95% CI) were obtained from stratified Cox proportional-hazards models. Relatives of ID individuals were compared to relatives of unaffected individuals. Structural equation modeling was used to estimate heritability.

Results: Relatives of ID individuals were at increased risk of ID compared to individuals with unaffected relatives. The RR of ID among relatives increased proportionally to the degree of genetic relatedness with ID probands; 256.70(95% CI 161.30–408.53) for monozygotic twins, 16.47(13.32–20.38) for parents, 14.88(12.19–18.16) for children, 7.04(4.67–10.61) for dizygotic twins, 8.38(7.97–8.83) for full siblings, 4.56(4.02–5.16) for maternal, 2.90(2.49–3.37) for paternal half-siblings, 3.03(2.61–3.50) for nephews/nieces, 2.84(2.45–3.29) for uncles/aunts, and 2.04(1.91–2.20) for cousins. Lower RRs were observed for siblings of probands with chromosomal abnormalities (RR 5.53, 4.74–6.46) and more severe ID (mild RR 9.15, 8.55–9.78, moderate RR 8.13, 7.28–9.08, severe RR 6.80, 5.74–8.07, and profound RR 5.88, 4.52–7.65). Male sex of relative and maternal line of relationship with proband was related to higher risk (RR 1.33, 1.25–1.41 for brothers vs. sisters and RR 1.49, 1.34–1.68 for maternal vs. paternal half-siblings). ID was substantially heritable with 0.95(95% CI 0.93–0.98) of the variance in liability attributed to genetic influences.

Conclusions: The risk estimates will benefit researchers, clinicians, families in understanding the risk of ID in the family and the whole population. The higher risk of ID related to male sex and maternal linage will be of value for planning and interpreting etiological studies in ID.

Discussion

Main findings

In this nationwide population-based study, we evaluated familial risk and heritability of ID. The sample of ID probands is 100 times bigger compared to the largest previous study on risk among siblings from British Columbia (Herbst & Baird, 1982). The use of several types of relatives allows evaluating the importance of genetic and environmental risk factors in the etiology of ID.

There are four main findings from our investigation. First, our 20-years risk and frequency of ID in full-siblings are comparable to old reports (Angeli & Kirman, 1975; Becker et al., 1977; Bundey & Carter, 1974; Bundey et al., 1989; Costeff & Weller, 1987; Durkin et al., 1976; Herbst & Baird, 1982; Laxova, Ridler, Bowen-Bravery, & Opitz, 1977; Turner et al., 1971; Turner & Partington, 2000). Now, we provide estimates with narrow confidence intervals also for halfsiblings and other relatives. Moreover, our study is first to report RR for ID comparing relatives of ID probands with relatives of unaffected individuals. High RR for monozygotic twins reflects ID characteristics with 0.9% prevalence and high heritability. Similar RR were reported for autism (Sandin et al., 2014), a disability with similar prevalence (1%–2%) and high (85%) heritability (Sandin et al., 2017).

Second, similar to the study by Bundey et al. (1989), we found no evidence for differences in familial risks related to comorbid medical conditions and adverse birth events, two probable biological mechanisms of ID. It is possible, that some of the birth complications traditionally considered as environmental risk factors reflect the response to genetic abnormalities in the fetus (Bolton et al., 1994; Simonoff, Bolton, & Rutter, 1996).

Third, our findings of an inverse relation between ID severity and the familial risk estimates are in accordance with older studies on siblings (Angeli & Kirman, 1975; Bundey & Carter, 1974; Durkin et al., 1976). We have observed a similar pattern of inheritance in second-degree relatives. A previous study by Reichenberg et al. (2016) showed a normal distribution of intellectual abilities among military conscripts who had siblings with severe ID. But those results are limited by the fact that individuals with medical diagnosis of ID are exempted from military assessment in Sweden and were not likely to be covered by the study. Our results showed a gradual risk decline in relation to level of intellectual impairment with shared etiological links across different levels of severity suggesting that the arbitrary cut-off for classifying ID severity into binary measure seems to be an oversimplification.

Forth, our data provide compelling evidence for the role of sex in familial risk of ID. In our study, we not only confirmed the higher risk for males compared to females in siblings of ID probands, but we also showed that similar sex differences were present in more distant relatives (Table S10). Higher prevalence of ID among males in comparison to females has been reported in population studies (Maulik et al., 2011) but studies in relatives produced ambiguous results, probably due to small sample size (Table S1). Our study confirms that, the sex differences observed in the general population are present in the relatives of ID probands, with males being more predisposed to ID. Matrilineallity was related to a higher risk in half-siblings and cousins of ID individuals in accordance with X-linked ID inheritance pattern.

Previous quantitative genetic methods focused on heritability of general (Kovas et al., 2013; Plomin & Deary, 2015) or low cognitive abilities within the normal range (Reichenberg et al., 2016). Heritability of ID as medical diagnosis has not been estimated before. The concordance in our study was as high as 73% for monozygotic, but relatively low of 9% for dizygotic twins. However, concordance is a measure on an absolute scale and depends on the disease prevalence in the population (Tenesa & Haley, 2013). With ID prevalence of 0.9%, genetic liability may be more accurately measured on a transformed scale by tetrachoric correlations where the liability for a disease is assumed to follow a standard normal distribution. The threshold on the liability distribution is estimated from the observed prevalence of the disease. Individuals are assumed to have a disease if they are above this threshold.

Further, severe ID is often linked to distinct genetic etiology caused by de novo mutations rather than polygenic traits associated with mild ID. In our study, tetrachoric correlations calculated separately for all ID levels and after exclusion of individuals with severe ID resulted in almost identical estimates, suggesting a low contribution of those phenotypes in ID heritability at the population level.

Heritability of ID was estimated to be 95%, considerably higher than 66%–86% reported for cognitive abilities in adulthood (Haworth et al., 2010; Panizzon et al., 2014). Those findings further highlighting importance of familial factors in diagnostics and etiological studies on ID. For future studies on the heritability of ID It is important to consider ‘maternal-effects in etiology’, previously described in quantitative genetic studies on general cognitive abilities (Devlin, Daniels, & Roeder, 1997). Substantially higher RR and 20-years risk estimates for maternal compared with paternal half-siblings were found in our study, suggesting that maternal factors may play an essential role also in clinically diagnosed ID.

Strengths and limitations

This study has several strengths, including the sample size, nationwide coverage, and access to both health and educational records. The ID prevalence of 0.9% in our study is close to 1% provided by the meta-analysis (Maulik et al., 2011). Swedish pediatric healthcare is publically funded with universal access to both primary and nonprimary healthcare (Wettergren, Blennow, Hjern, Soder, & Ludvigsson, 2016). A large number of relatives of ID probands allowed us to provide precise estimates of familial risk for several types of kinship. The RRs in this article are the first estimated for ID using a reference from the general population. We do however acknowledge some limitations. First, our study focused only on Swedish born individuals, not including immigrants. Second, despite the universal access to health care we cannot eliminate the possibility that socially disadvantaged groups such as individuals with substance misuse, experiencing homelessness or involved with justice system, could be less likely to seek psychiatric care and ID can remain underdiagnosed. Also, differences in behavioral manifestation and comorbid disorders between females and males with ID may diminish the likelihood of diagnosing ID in females.

Third, data retrieved from registers are subject to left-censoring with missing data prior to data collection. In our study, the actual time point for ID diagnosis might be earlier then the first record of ID diagnosis. For example, HURPID provides information on the date of graduation from upper secondary schools for pupils with ID (typically after the age of 18 year), not the genuine date of ID diagnosis. Similarly, the precise date of diagnosis is not available for ID individuals diagnosed in outpatient care prior to 2001, when those data has been included in NPR. Those factors can lead to either over-or underestimation of familial risk. Some bias towards higher risk estimates may be present due to assortative mating described for cognitive abilities (Plomin & Deary, 2015).

Conclusions and clinical implications

The findings are of value for planning and interpreting etiological studies in ID. This study provided strong evidence on the familial etiology of ID, mostly related to genetic factors. Precise and up-to-date risk estimates provided by this study will benefit clinicians and families in understanding the risk of ID in the family and the whole population. The significant familial loading in ID suggests that the vulnerabilities of family members should be taken into account in intervention programs in ID.

Gender differences in fresh vegetable intake from 1979 to 2017 in low sex-inequality Finland: The magnitude of the gap between genders doubled across the study period

Kähäri, A. (2021), "Gender differences in fresh vegetable intake from 1979 to 2017 in Finland", British Food Journal, Dec 28 2021. https://doi.org/10.1108/BFJ-09-2021-1004

Abstract

Purpose: Previous research has shown that in contemporary societies, women have a healthier dietary intake than men. However, no research has examined how this gender gap develops over the long term. The present study examined how gender differences in fresh vegetable intake frequency have evolved from 1979 to 2017 in Finland and whether differences are affected by age or educational level.

Design/methodology/approach: The data were derived from annually repeated, nationally representative “Health Behaviour and Health among the Finnish Adult Population” and “Regional Health and Well-being (RHW)” surveys on the health habits of the Finnish population. The dataset is a time series of repeated cross-sectional surveys. In total, the data sample comprised 161,996 Finns aged 20–64 years. Descriptive methods and logistic regression were used for the analysis.

Findings: During 1979–2017, the prevalence of daily vegetable intake increased from 12 to 35% among men and from 18 to 56% among women. Thus, the magnitude of the gap between genders doubled across the study period. The increased vegetable intake was partly explained by the changing education and age structures of society. Potential explanations and avenues for future research are also discussed. Policy implications depend on whether the findings are interpreted as a case of health differences or health inequality.

Originality/value: This study used a long time series to analyse how gender differences in vegetable intake have evolved in a Nordic welfare state context. It showed that the gap in fresh vegetable intake between men and women has widened.

There exist fundamental geometrical principles that result from the inherent interplay between movement and organisms’ internal representation of space: Animals spontaneously reduce the world into a series of sequential binary decisions

The geometry of decision-making in individuals and collectives. Vivek H. Sridhare et al. Proceedings of the National Academy of Sciences, December 14, 2021 118 (50) e2102157118; https://doi.org/10.1073/pnas.2102157118

Significance: Almost all animals must make decisions on the move. Here, employing an approach that integrates theory and high-throughput experiments (using state-of-the-art virtual reality), we reveal that there exist fundamental geometrical principles that result from the inherent interplay between movement and organisms’ internal representation of space. Specifically, we find that animals spontaneously reduce the world into a series of sequential binary decisions, a response that facilitates effective decision-making and is robust both to the number of options available and to context, such as whether options are static (e.g., refuges) or mobile (e.g., other animals). We present evidence that these same principles, hitherto overlooked, apply across scales of biological organization, from individual to collective decision-making.

Abstract: Choosing among spatially distributed options is a central challenge for animals, from deciding among alternative potential food sources or refuges to choosing with whom to associate. Using an integrated theoretical and experimental approach (employing immersive virtual reality), we consider the interplay between movement and vectorial integration during decision-making regarding two, or more, options in space. In computational models of this process, we reveal the occurrence of spontaneous and abrupt “critical” transitions (associated with specific geometrical relationships) whereby organisms spontaneously switch from averaging vectorial information among, to suddenly excluding one among, the remaining options. This bifurcation process repeats until only one option—the one ultimately selected—remains. Thus, we predict that the brain repeatedly breaks multichoice decisions into a series of binary decisions in space–time. Experiments with fruit flies, desert locusts, and larval zebrafish reveal that they exhibit these same bifurcations, demonstrating that across taxa and ecological contexts, there exist fundamental geometric principles that are essential to explain how, and why, animals move the way they do.

Keywords: ring attractormovement ecologynavigationcollective behaviorembodied choice

      Model Features That Determine Network Behavior

There are key features that are essential to produce the bifurcation patterns observed in our data (i.e., for any decision-making system to break multichoice decisions to a series of binary decisions).

• 1) Feedback processes that provide the system directional persistence and drive such bifurcations are crucial to exhibit the observed spatiotemporal dynamics. In the neural system, this is present in the form of local excitation and long-range/global inhibition (7, 18, 19). However, as shown in our model of collective animal behavior below, we expect that similar dynamics will be observed if the necessary feedbacks are also incorporated into other models of decision-making, such as to PDF sum–based models, for example (20).

• 2) Observing similar decision dynamics requires a recursive (embodied) interplay between neural dynamics and motion in continuous space. Here, the animal’s geometrical relationship with the targets changes as it moves through physical space. Since neural interactions depend on this changing relationship, space provides a continuous variable by which the individual traverses the time-varying landscape of neural firing rates.

These essential features, along with the observed animal trajectories in the two-choice context, are reminiscent of collective decision-making in animal groups [models (41⇓⇓⇓–45), fish schools (46), bird flocks (47), and baboon troops (26)]. Below, we consider an established model of collective decision-making (41) to draw links between these two scales of biological organization—decision-making in the brain and decision-making in animal groups.

Why It Is Hard to Be Happy with What We Have... Habituation to positive changes in lifestyle and constant comparisons leave us unhappy even in the best of conditions. Why?

Dubey, Rachit, Tom Griffiths, and Peter Dayan. 2021. “Why It Is Hard to Be Happy with What We Have: A Reinforcement Learning Perspective.” PsyArXiv. December 31. doi:10.31234/osf.io/8jd2x

Abstract: The pursuit of happiness is not easy. Habituation to positive changes in lifestyle and constant comparisons leave us unhappy even in the best of conditions. Given their disruptive impact, it remains a puzzle why habituation and comparisons have come to be a part of cognition in the first place. Here, we present computational evidence that suggests that these features might play an important role in promoting adaptive behavior. Using the framework of reinforcement learning, we explore the benefit of employing a reward function that, in addition to the reward provided by the underlying task, also depends on prior expectations and relative comparisons. We find that while agents equipped with this reward function are less "happy", they learn faster and significantly outperform standard reward-based agents in a wide range of environments. The fact that these features provide considerable adaptive benefits might explain why we have the propensity to keep wanting more, even if it contributes to depression, materialism, and overconsumption.

Discussion

Sensibly or not, people often find it hard to remain happy with what they have. One enjoys a newly bought car for a time, but over time it brings fewer positive feelings and one eventually begins dreaming of the next rewarding thing to pursue. As a consequence, we keep getting lured by the promise of unfathomable future happiness whilst hardly enjoying the riches of the present. Here, we have presented a series of simulations that suggest that these seemingly maladaptive “flaws” might perhaps play an important role in promoting adaptive behavior. Using the idea of reward design, we explored the value of adaptive expectations and relative comparisons as a useful reward signal and found that across a wide range of environments, these features help an agent learn faster and be more robust to changes in the environment. Thus, even though comparisons to the past and future often induce unhappiness, they might still motivate one to strive to escape the unpleasant or (even worse) mundane present.

While relative comparisons were generally advantageous, we also found that they can be quite harmful in certain settings. For instance, in an environment with many similar options, comparisons resulted in constant dissatisfaction without any improvement in performance (Exp 2a). Thus, one lesson that can be taken from our results is that when presented with many similar choices, a decision-maker is better off curtailing comparisons and making decisions without relying on them. This also accords with the view that given the explosion of choices in modern times, learning to accept good enough will increase satisfaction and simplify decision-making35, 67. However, this leaves an open question about how a decision-maker can come to manage and curtail comparisons in the first place. Future research should investigate possible mechanisms via which an agent can set and learn its own aspiration level, which can then provide insights on how to design interventions to reduce comparisons. A promising direction in this vein could be studying how aspiration levels might be shaped via a functional relationship between a model-free and model-based system68, 69. For instance, a model-based system might alter the aspiration level of the model-free system based on fluctuations in the environment. This in turn could also be helpful to understand what leads someone to develop unreasonably high aspirations70–72 .

We observed that an agent’s internal happiness was not necessarily reflective about their performance in the environment and both being ‘too happy’ and ‘too unhappy’ led to unwanted outcomes. Agents with unreasonably high aspiration levels developed sub-optimal behavior and were also very ‘unhappy’ in their lifetimes (due to unmet aspirations). Similarly, agents that had a very low aspiration level also performed poorly as they were prone to getting stuck at a local minimum. However, these agents, despite accumulating very low objective rewards, were ‘very happy’ in their lifetimes. Together, these findings provide computational support to a growing body of research which documents the “dark side” of being too happy and are consistent with early philosophical ideas that extreme levels of any emotion, including happiness, can be undesirable73–75. Further, our finding that ‘moderately unhappy’ agents obtain the highest objective rewards can be loosely compared to the finding that people who experience slightly 21/31 lower levels of happiness are more successful in terms of income and education level compared to people with the highest levels of happiness76 .

Our results also speak to a literature in economics that explores the types of evolutionary pressures that could have produced habituation and relative consumption77–80. Similar to our work, these studies model happiness using the metaphorical principal-agent framework, where the principal (evolution) wishes the agent to be maximally fit and has the ability to choose the utility function of the agent to her best advantage. One such study shows that when an agent has limited ability to make fine distinctions (i.e., it cannot tell apart two values that are within a small distance from each other) and when it has a limited range of utility levels (i.e., it has a bound on the minimum and maximum level of happiness it can experience), then evolution would favor a utility function that is adaptive and depends on relative comparisons78.In our view, the primary contribution of these studies is showing how cognitive limitations could have favored a happiness function that depends on prior expectations and relative comparisons, and our work complements these studies by suggesting that, regardless of the agent’s constraints, this function could have also been favored because of the learning advantages it confers.

Closely related to our research is recent work that posits a role for mood in learning81–84. In these proposals, mood is formalized as the moving average of reward prediction errors (and more recently, an estimate of the Advantage function84), and is considered to represent environmental momentum. Momentum indicates whether an environment is improving or worsening and can be an important variable for adaptive behavior. Our results augment these studies by showing how (myopic) reward prediction errors (in the form of prior expectations) are a valuable aid to relative comparisons and accelerate learning in a wide variety of environments. Studying the interaction of mood with prior expectations and relative comparisons is an important question for future work.

One observation in the context of mood is that the sorts of adaptive relativities for learning that we have discussed can lead to instabilities in evaluation - modeling aspects of dynamic diseases, such as bipolar disorder81. Certainly, the subjective values of states that are taught by the subjective reward functions can vary greatly from their objective values, which is problematic if, for instance, the parameters of the subjective reward function change over time. More generally, it would be worth exploring whether dysfunctions such as anhedonic depression85–87 partly arise because of problems with subjective rather than objective components of reward sensitivity. The same issues might be more broadly relevant, given the chain of reasoning that leads from disturbed average rates of reward88 to altered motivation in depression89, potentially negative symptoms in schizophrenia90, and indeed transdiagonistically across a number of psychiatric and neurological conditions91. Nevertheless, it would be remiss not to point out the careful distinctions made between hedonic and motivational aspects of rewards, as between ’liking’ and ’wanting’52, 53, that we have blurred.

Our work has several limitations which should be addressed in order to draw more concrete parallels between our simulation-based results and psychological research on happiness. For one, we assumed that the agent designer directly provided the reward function to the agent and the agent had no say in what reward function it received. This simplification meant that we were not able to study how an agent might develop biased expectations or aspirations as well as study the consequences of an agent being able to control its own happiness. A productive avenue for future research could be studying reward design using the meta-learning framework, such that an agent learns to choose the parameters of its happiness function in response to the environment it faces92, 93. Relatedly, we also did not investigate in detail the potential interaction of discounting with prior expectations and relative comparisons (since we kept a fixed value for the discount factor in our experiments). Studying this further would be an important question for the future. 22/31 Another limitation of our work is that we did not consider how aspirations can be influenced by social comparisons. Future research could address this by conducting multi-agent simulations wherein agents also compare themselves to other agents in the environment. This could also help understand how relative comparisons might interact with other components of happiness such as guilt and jealousy. Future work should also consider how the components of happiness we have considered here might interact with other affective states such as anxiety94 and boredom95. Lastly, while our choice of environments was driven in part due to their popularity within the RL community, it is not completely clear how much our results will generalize to more real-world situations and therefore, caution must be exercised when generalizing our simulation results.

We conclude by providing some perspective on the problem of overconsumption, an extremely pressing issue that severely threatens future generations. Constant habituation to modern luxuries and ever-rising aspirations are leading us to consume Earth’s natural resources at an alarming rate and resulting in rapid deterioration of our planet96–100. Paradoxically, people in modern societies are hardly more satisfied than previous generations101–104, yet we keep becoming caught in the rat race of consumption and continuing the modern obsession of growth at all costs105–109. One implication of our results is that given how advantageous habituation and relative comparisons are in promoting adaptive behavior, it could be possible that these features might be very deeply entrenched in our minds. Thus, any steps to reduce overconsumption will also need serious considerations on how to tackle these biases of the human mind and will require the expertise of scientists from multiple disciplines. For better or worse, we are prone to becoming trapped in a cycle of never-ending wants and desires, and it is more urgent than ever to develop concrete policies and large-scale interventions to reduce habituation and comparisons.

US Economists: Increased consensus on many economic propositions, specifically the appropriate role of fiscal policy in macroeconomics and issues surrounding income distribution; another area of consensus is concern with climate change

Consensus among economists 2020 – A sharpening of the picture. Doris Geide-Stevenson and Alvaro La Parra Perez. Weber State Univ, December 2021. https://t.co/NdkWtZOUQH

Abstract: Based on an extensive survey of the members of the American Economic Association this paper compares consensus among economists on a number of economic propositions over four decades. The main result is an increased consensus on many economic propositions, specifically the appropriate role of fiscal policy in macroeconomics and issues surrounding income distribution. Economists now embrace the role of fiscal policy in a way not obvious in previous surveys and are largely supportive of government policies that mitigate income inequality. Another area of consensus is concern with climate change and the use of appropriate policy tools to address climate change.