BST hypothesises that genes influence weight at least partly through their effects on appetite—i.e. there is variation in appetite that has a strong genetic basis, and variation in appetite causes differences in body weight. The idea that appetite plays a causal role in obesity is not new; it was first proposed by Stanley Schachter in 1968 . In a series of innovative experiments, he observed that obese adults ate significantly more than healthy weight adults when the food on offer was highly palatable, but showed no difference in intake in response to bland foods. At the same time, obese adults did not show the same compensatory down-regulation of food intake following a high-calorie snack as normal-weight adults, indicating blunted satiety (fullness) or an overriding of satiety. Schachter came up with externality theory to explain these observations. He proposed that obese individuals have two distinct aberrations in appetite regulation that lead to overeating; they are overly responsive to highly palatable food cues (wanting to eat (or eat more) in response to the sight, smell and taste of palatable food) and are under-responsive to internal satiety mechanisms (fullness).
Wardle was the first to make the link between these appetitive characteristics identified by Schachter and genetic risk of obesity. She developed the BST in which she hypothesised that genes influence weight at least partly via biological mechanisms that control appetite regulation . The BST explains how human body weight can have both genetic and environmental drivers at the same time and why genetic expression on weight is likely to be stronger in more ‘obesogenic’ environments (see Fig. 1). Individuals who are genetically predisposed to be highly responsive to food cues are more likely to overeat in an environment in which food cues pervade every aspect of daily living. Those predisposed to weaker satiety signals are more likely to overeat in response to larger portion sizes and multiple opportunities to eat.
Development of Psychometric Measures of Appetite for Children
In order to test the BST, Wardle needed to measure these appetitive characteristics in samples large enough to establish reliable associations with weight, demonstrate generalisability and estimate genetic influence. Laboratory-based measures of appetite provide unparalleled detail, but the time and expense incurred prohibit measuring eating behaviour objectively in large samples. Another limitation is that only a single ‘snapshot’ of eating behaviour is captured, and behaviour is subject to any extraneous factors at play during the time of testing. The unfamiliar setting and not liking the test food can be particularly problematic. Wardle also saw limitations to studying the BST in adults and considerable advantages to undertaking research with infants and children. Adults with longstanding obesity may have abnormalities in appetite as a result of physiological changes caused by the excess weight itself, and overweight adults are often dieting. Young children are unlikely to be dieting and are too young to have experienced long-term effects of chronic obesity. Studying infants prospectively into childhood provides the opportunity to study the cause-effect relationship between appetite and weight as it starts to emerge.
Wardle therefore developed the Child Eating Behaviour Questionnaire (CEBQ), a comprehensive parent-report psychometric measure of a range of children’s appetitive characteristics, to test the BST in large samples of children . While standardised psychometric measures lose the objectivity of laboratory-based observations, they have the advantage of characterising habitual eating behaviour over many meals and situations—in this respect, such measures capture the enduring appetitive ‘trait’ rather than a ‘state’ of hunger or fullness at the time of testing. Young children lack the comprehension skills or self-awareness to answer questions about their own behaviour, but parents tend to know them very well, arguably making them the most accurate informants of their children’s behaviour. Parent report is of course subjective and has the potential for bias, but the CEBQ has been validated against objectively measured eating behaviour .
The CEBQ is a comprehensive measure of all observable aspects of children’s eating behaviour hypothesised to play a causal role in overweight or to protect against overweight. Parents respond to items that describe a range of eating behaviours using a five-point frequency scale (‘never’, ‘rarely’, ‘sometimes’, ‘often’, ‘always’) to indicate the frequency with which their child demonstrates each behaviour. Two scales characterise Schachter’s behavioural measures of responsivity to food cues and are hypothesised to predispose to overweight: ‘food responsiveness’ measures a child’s tendency to want to eat when prompted by palatable foods (e.g. ‘even if my child is full up, s/he finds room for his/her favourite food’), and ‘enjoyment of food’ captures the subjective reward experienced while eating (e.g. ‘my child enjoys eating’); higher scores on these scales indicate a more avid appetite. Two other scales characterise Schachter’s behavioural measures of responsivity to internal satiety cues and are hypothesised to protect against overweight: ‘satiety responsiveness’ measures a child’s fullness threshold (e.g. ‘my child gets full before his/her meal is finished’) and ‘slowness in eating’ captures the pace with which a child finishes a meal, with higher eating speed hypothesised to outpace biological satiety mechanisms (e.g. ‘my child takes more than 30 min to finish a meal’); higher scores on these scales indicate better appetitive control. Two scales measure the tendency to either under- or overeat in response to negative emotions: ‘emotional overeating’ is thought to predispose to overweight (e.g. ‘my child eats more when worried’), and ‘emotional undereating’ is hypothesised to protect against overweight (e.g. ‘my child eats less when upset’). ‘Food fussiness’ assesses the tendency for a child to be highly selective about what they will agree to eat and captures both refusal to try unfamiliar foods (termed ‘neophobia’, e.g. ‘my child refuses new foods at first’) as well as pickiness about the textures and tastes of familiar foods (e.g. ‘my child is difficult to please with meals’). Fussiness is a common characteristic of children who fail to thrive, because they often eat too little; this trait may therefore offer some protection against overweight.
The CEBQ scales have good internal and external reliability  and show strong tracking from early to late childhood  indicating that they characterise fairly stable traits that persist over development. The CEBQ has also been adapted to measure appetitive traits during infancy (the Baby Eating Behaviour Questionnaire, BEBQ ), and more recently in adulthood (the Adult Eating Behaviour Questionnaire, AEBQ ). The BEBQ measures four of the same appetitive traits during the period of exclusive milk feeding, before any solid food has been introduced: ‘food responsiveness’, ‘enjoyment of food’, ‘satiety responsiveness’ and ‘slowness in eating’. The AEBQ is a self-report version of the CEBQ for adults, capturing largely the same appetitive traits as the CEBQ: ‘food responsiveness’, ‘enjoyment of food’, ‘satiety responsiveness’, ‘slowness in eating’, ‘emotional overeating’, ‘emotional undereating’ and ‘food fussiness’, but with the addition of a ‘hunger’ scale to capture experienced levels of hunger (arguably only possible via self-report) . Together, these three measures enable assessment of eating behaviour across the life course from infancy (BEBQ) and childhood (CEBQ) into adulthood (AEBQ).
The development of these psychometric measures of appetite has led to the emergence of an extensive literature exploring the relationship between appetite and weight in large population-based samples, the genetic basis of appetite and the role of appetite in mediating genetic risk of obesity. The majority of research has focused on the scales that characterise the appetitive traits relating to Schachter’s externality theory, ‘food responsiveness’ and ‘enjoyment of food’ (indexing hyper-responsiveness to external food cues) and ‘satiety responsiveness and slowness in eating’ (indexing blunted responsiveness to internal satiety cues).
Variation in Appetitive Traits Drives Weight Gain
A wealth of cross-sectional research with the CEBQ has established almost without exception that ‘food responsiveness’ and ‘enjoyment of food’ are positively and ‘satiety sensitivity’ and ‘slowness in eating’ are negatively associated with measures of adiposity, in different samples of children ranging from 3 to 13 years of age [31,32,33,34,35,36]. Importantly, studies have also demonstrated that these appetitive traits influence weight across the whole spectrum in a graded fashion. They do not simply distinguish the clinically obese from the ‘healthy weight’ children, but explain more subtle variation in weight as well, e.g. between children at the lower versus higher end of ‘healthy weight’ [31,35,, 32, 34–36].
This research provides support for the BST insofar as greater adiposity is characterised by distinctive eating behaviours that predispose to overeating, but cross-sectional data cannot provide any insight into the direction of the relationship between appetite and weight. Establishing the cause-effect relationship is not a straightforward task. It is not possible to randomise individuals to be more or less food responsive or satiety sensitive, and then examine the impact on weight. An alternative approach is to use prospective data to establish if variation in appetite predicts weight gain better than variation in weight predicts appetite change. The BST also hypothesises that these appetitive traits, like body weight itself, have a genetic basis.
Wardle established a large population-based prospective birth cohort of 2402 infant twin pairs, Gemini , to explore genetic and environmental influence on early growth, with a focus on behavioural pathways. Two design features ensure that the Gemini cohort is well placed to examine the validity of the BST: (i) it is a prospective birth cohort allowing the direction of the relationship between appetite and weight to be tracked as it starts to emerge in early life and (ii) the twin design allows the genetic and environmental influence on appetite to be explored.
Gemini was the first study to examine the (bidirectional) prospective relationships between appetite and weight from birth. Data strongly supported the hypothesis that variation in appetite at 3 months was driving early weight gain from 3 to 15 months, not the other way around (weight variation at 3 months did not predict appetite change from 3 to 15 months) . A follow-up study strengthened this finding, by comparing the growth trajectories from 3 to 15 months of twin pairs discordant for ‘food responsiveness’ (n = 121 pairs) and ‘satiety responsiveness’ (n = 172 pairs). This design enabled an investigation of the relationship between appetite and weight gain while controlling for important environmental confounders that are completely shared by twin pairs (e.g. maternal pre-pregnancy weight, gestational weight gain, maternal diet during pregnancy, SES). The weights of the twin pairs diverged progressively such that by 15 months of age, there was a 1-kg difference, equating to a 10% difference in body weight [39••]. The only subsequent prospective study of 210 infants from Singapore also found that higher ‘food responsiveness’ and lower ‘satiety responsiveness’ (and ‘slowness in eating’) were associated with greater infant weight gain .
Appetitive Traits Mediate Genetic Influence on Weight
Using the BEBQ, Gemini has also established the relative contribution of genetic and environmental influence to variation in appetitive characteristics during the earliest period of life, when infants are still exclusively milk-fed . Heritability was substantial for each of ‘enjoyment of food’ (53%), ‘food responsiveness’ (59%), ‘satiety responsiveness’ (72%) and ‘slowness in eating’ (84%). This finding is striking, given that the BEBQ captures variation in appetite for milk only—even very early in life infants vary considerably in their appetite, and this variation is both associated with weight gain and is genetically based. A follow-up study to quantify the extent to which there is genetic overlap between appetite and weight at 3 months found that approximately one third of the genetic influences underlying 3-month weight are the same as those underlying appetite, supporting the hypothesis that genes influence weight partly through effects on appetite .
The infant study in Gemini followed only one previous examination of the heritability of ‘enjoyment of food’ and ‘satiety responsiveness’ in a very large population-based sample of 10-year-old twin children (n = 5435 pairs) from the Twins Early Development Study (TEDS), also conducted by Wardle . The heritability estimates observed in older children were of the same magnitude as those observed in infancy for both ‘enjoyment of food’ (75%) and ‘satiety responsiveness’ (63%). Eating speed, measured objectively in a subsample of the children (n = 254), also showed high heritability (62%) .
The recent discovery of common genetic variants associated with human body weight has opened up new avenues for detailed examinations of the mechanisms involved, and the likely role of appetite. Shortly after the discovery of FTO, Wardle and her colleagues  used data from TEDS to show that 10-year-old children who carried at least one copy of the lower risk variant (TT or AT) were significantly more satiety sensitive than those carrying two copies of the higher-risk version (AA). This effect remained after adjustment for BMI, indicating that FTO is influencing body weight via impacting satiety sensitivity. This study was replicated using a behavioural measure of satiety sensitivity in a subsample of the children at 5 years of age  and shown independently by Cecil and colleagues . A more recent study [48••] showed that a composite genetic risk score both with and without FTO was associated with ‘satiety responsiveness’ in the TEDS children at 10 years of age, and mediated part of the association between the genetic risk score and adiposity, indicating that FTO and other variants are affecting adiposity partly via mechanisms that regulate satiety.
In three other large independent samples of adults (n = 4632, n = 1231 ; n = 3852 ), questionnaire measures of ‘uncontrolled eating’ (a measure of extreme hunger and eating trigged by external food cues) and ‘emotional eating’ were also associated with genetic risk of obesity, and these appetitive traits mediated part of the association between the genetic risk score and adiposity . Gene expression studies have also strongly supported an appetitive pathway insofar as many of the common risk variants are in or near genes that are highly expressed in the hypothalamus and pituitary gland, key sites of central appetite regulation [17••].
The magnitudes of the associations between known obesity-related genetic variants and appetitive traits (and body weight itself) are often disappointingly small, but identifying the mechanisms is nevertheless an important endeavour. Establishing causal pathways can guide researchers towards targeted interventions to reduce obesity risk. The evidence for genetic risk of obesity operating (at least partly) via appetitive mechanisms suggests that behavioural processes may serve as useful intervention targets.
Behavioural Expressions of Appetitive Traits and Weight Gain
A key question of interest has been how these genetically determined appetitive traits lead to weight gain in response to the current ‘obesogenic’ environment. In other words, what are the behavioural expressions of these traits that lead to overeating and weight gain in an everyday context? Recent research in Gemini has established that greater responsiveness to food cues and blunted satiety sensitivity are characterised by distinctive (different) ‘everyday’ patterns of excess intake, in very young children. When the twins were approximately 2 years old, parents completed 3-day diet diaries for 2203 of the children . These data were used to derive two possible patterns of overeating—consuming a larger average meal size at each eating occasion and eating more frequently throughout the day. Relationships between these intake patterns and appetite (‘food responsiveness’ and ‘satiety responsiveness’ measured using the CEBQ at 15 months) were explored. More food responsive children ate more frequently throughout the day but did not eat a larger amount each time [52•]. On the other hand, children with impaired satiety sensitivity consumed larger average meal sizes each time they ate, but did not eat more frequently throughout the day [52•]. These distinctive patterns of overconsumption make sense given what we know about the interaction between appetite and environmental opportunity. Individuals who are highly responsive to food cues are likely to eat more often in response to an environment where food cues are encountered throughout the day. Those with weaker satiety signals are susceptible to overeating in response to larger portion sizes, because they take longer to feel full (or require more energy or a larger sized portion (higher grams) of food).
Subsequent research showed that consuming larger average meal sizes, but not eating more frequently, was the key driver of excessive weight gain from 2 to 5 years of age. But it is important to understand the relative contribution of meal size and meal frequency to weight gain in older children who have more autonomy over how much and how often they eat [53•].