Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed

Abstract Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).

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The quantitative genetics of the endemic prevalence of infectious diseases: Indirect Genetic Effects dominate heritable variation and response to selection

10.1101/2021.04.07.438789 ◽

2021 ◽

Author(s):

Piter Bijma ◽

Andries Hulst ◽

Mart C. M. de Jong

Keyword(s):

Infectious Disease ◽

Infectious Diseases ◽

Disease Status ◽

Host Population ◽

Genetic Effects ◽

Breeding Value ◽

Response To Selection ◽

Heritable Variation ◽

Genetic Theory ◽

Quantitative Genetic

AbstractPathogens have profound effects on life on earth, both in nature and agriculture. Despite the availability of well-established epidemiological theory, however, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of the transmission dynamics of infectious diseases for heritable variation and response to selection of the host population, our current theoretical framework of quantitative genetics does not include these dynamics. As a consequence, we do not know which genetic effects of the host population determine the prevalence of an infectious disease, and have no concepts of breeding value and heritable variation for endemic prevalence.Here we propose a quantitative genetic theory for the endemic prevalence of infectious diseases. We first identify the genetic factors that determine the prevalence of an infectious disease, using an approach founded in epidemiological theory. Subsequently we investigate the population level effects of individual genetic variation on R0 and on the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for both prevalence and individual binary disease status, and show how these parameters depend on the endemic prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases when prevalence approaches zero, while heritability of individual disease status goes to zero. We show that response of prevalence to selection accelerates considerably when prevalence goes down, in contrast to predictions based on classical genetic models. Finally, we show that most of the heritable variation in the endemic prevalence of the infection is due to indirect genetic effects, suggestion a key role for kin-group selection both in the evolutionary history of current populations and for genetic improvement strategies in animals and plants.

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The quantitative genetics of the prevalence of infectious diseases: hidden genetic variation due to Indirect Genetic Effects dominates heritable variation and response to selection

Genetics ◽

10.1093/genetics/iyab141 ◽

2021 ◽

Author(s):

Piter Bijma ◽

Andries D Hulst ◽

Mart C M de Jong

Keyword(s):

Genetic Variation ◽

Infectious Diseases ◽

Quantitative Genetics ◽

Disease Status ◽

Genetic Effects ◽

Breeding Value ◽

Response To Selection ◽

Heritable Variation ◽

Genetic Theory ◽

Quantitative Genetic

Abstract Infectious diseases have profound effects on life, both in nature and agriculture. However, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of transmission of infections for heritable variation and response to selection, current quantitative genetics ignores transmission. Thus, we lack concepts of breeding value and heritable variation for endemic prevalence, and poorly understand response of endemic prevalence to selection. Here we integrate quantitative genetics and epidemiology, and propose a quantitative genetic theory for the basic reproduction number R0 and for the endemic prevalence of an infection. We first identify the genetic factors that determine the prevalence. Subsequently we investigate the population level consequences of individual genetic variation, for both R0 and the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for endemic prevalence and individual binary disease status, and show that these depend strongly on the prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases strongly when prevalence decreases, while heritability of disease status approaches zero. As a consequence, response of the endemic prevalence to selection for lower disease status accelerates considerably when prevalence decreases, in contrast to classical predictions. Finally, we show that most heritable variation for the endemic prevalence is hidden in indirect genetic effects, suggesting a key role for kin-group selection in the evolutionary history of current populations and for genetic improvement in animals and plants.

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58 Integrating Quantitative Genetics and Epidemiology: Why Selection Against Infectious Diseases Is More Promising Than We Think

Journal of Animal Science ◽

10.1093/jas/skab235.054 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 31-32

Author(s):

Piter Bijma ◽

Piter Bijma

Keyword(s):

Infectious Diseases ◽

Genetic Parameters ◽

Genetic Variance ◽

Disease Status ◽

Genetic Theory ◽

Breeding Values ◽

Quantitative Genetic ◽

The Mean ◽

Low Prevalence ◽

Simple Average

Abstract Pathogens have profound effects on livestock. The low heritabilities of individual binary disease status suggest limited prospects for genetic improvement. However, a proper quantitative genetic theory for infectious diseases, including transmission dynamics, is currently lacking. Here we present a quantitative genetic theory for endemic infectious diseases, focussing on the genetic factors that determine the prevalence (P; the mean fraction of the population that is infected). We present simple expressions for breeding values and genetic parameters for the prevalence. Without genetic variation in infectiousness, breeding values for prevalence are a factor 1/P greater than the ordinary breeding values for individual binary disease status (0/1). Hence, even though prevalence is the simple average of individual binary disease status, breeding values for prevalence show much greater variation than our ordinary breeding values. This implies that the genetic variance that determines the potential response of prevalence to selection is largely due to indirect genetic effects (IGE), and thus hidden to ordinary genetic analysis and selection. Hence, the genetic variance that determines the potential of livestock populations to respond to selection must be much greater than currently believed, particularly at low prevalence. We evaluated this implication using simulation of endemics following standard methods in epidemiology. Results show that response of prevalence to selection increases very strongly when prevalence decreases, and is much greater than predicted by our ordinary breeding values. These results supports our theoretical findings, and show that selection against infectious diseases is much more promising than currently believed.

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GENETIC SELECTION FOR AND EVALUATION OF NONDIAPAUSE LINES OF PREDATORY MIDGE, APHIDOLETES APHIDIMYZA (RONDANI) (DIPTERA: CECIDOMYIIDAE)

The Canadian Entomologist ◽

10.4039/ent118869-9 ◽

1986 ◽

Vol 118 (9) ◽

pp. 869-879 ◽

Cited By ~ 20

Author(s):

Linda A. Gilkeson ◽

Stuart B. Hill

Keyword(s):

Sex Ratio ◽

Selection Pressure ◽

Gradual Increase ◽

Genetic Selection ◽

Response To Selection ◽

Aphidoletes Aphidimyza ◽

Selected Lines ◽

Line Selection ◽

Selection For ◽

Diapause Incidence

AbstractFour lines of Aphidoletes aphidimyza (Rond.) were selected for nondiapause (one for 50 generations) under L:D 8:16 and 21 ± 1°C. In three selected lines, diapause incidence dropped rapidly in the first four or five generations, with means of 3–11% thereafter. There was no clear response to selection in the fourth line. Neither morphology nor sex ratio was affected by nondiapause selection in any lines, nor was fecundity affected in the longest-reared line. Reciprocal crosses indicated that the diapause trait was dominant; the effect of relaxing selection pressure was a gradual increase in diapause incidence after eight generations. There was a correlation between increased diapause incidence and slower development in selected lines. Diapause larvae took longer to develop than nondiapause larvae from the same line. Selection for nondiapause under L:D 8:16 with fluctuating thermoperiods was unsuccessful.

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