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. Author manuscript; available in PMC: 2024 Feb 9.
Published before final editing as: Br J Psychiatry. 2021 Jul 23:1–8. doi: 10.1192/bjp.2021.104

Comorbidity between types of eating disorders and general medical conditions

Natalie C Momen 1, Oleguer Plana-Ripoll 2, Cynthia M Bulik 3, John McGrath 4, Laura M Thornton 5, Zeynep Yilmaz 6, Liselotte Vogdrup Petersen 7
PMCID: PMC10853638  NIHMSID: NIHMS1952236  PMID: 35049471

Abstract

Background:

Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorders.

Aims:

To provide relative and absolute risks of bidirectional associations of (a) anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified with (b) a range of general medical conditions.

Methods:

We included all people born in Denmark 1977-2010. We collected information on eating disorders and considered the risk of subsequent general medical conditions, using Cox-proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered prior general medical conditions and subsequent eating disorders.

Results:

An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a general medical condition ranged from 0.94 (95% CI: 0.57-1.55) to 2.05 (95% CI: 1.86-2.27). For those with a prior general medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI: 1.26 to 1.45) to 1.98 (95% CI 1.71 to 2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared to reference groups.

Conclusions:

This is the largest and most detailed examination of eating disorder-general medical condition comorbidity. The findings indicate general medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.

Keywords: eating disorders, comorbidity, register-based research, epidemiology, anorexia nervosa, bulimia nervosa

INTRODUCTION

Comorbidity

Prevalence of somatic illnesses is higher in individuals with psychiatric disorders than in those without.1–4 The relation appears to be bidirectional, with subsequent diagnoses of general medical conditions (MCs) increased in those with psychiatric disorders and, among those identified with MCs, an increased risk of certain psychiatric disorders.2,4 Eating disorders (EDs) have both long-term somatic consequences as well as high somatic comorbidity and mortality;5,6 however, the nature of the associations is unclear.

Previous research

Two studies that explored a broad range of MCs following ED diagnosis found increased risk for almost all studied MCs.1,3 A third evaluated the association in both directions, finding a mix of increased and decreased risks for both subsequent MCs in those with EDs, and subsequent EDs in those with MCs.4 EDs represent distinct psychiatric conditions with unique precipitating factors and physical sequelae. They include a heterogeneous group of conditions (i.e., anorexia nervosa [AN], bulimia nervosa [BN], and eating disorders not otherwise specified [EDNOS]), which may carry differential risk for various MCs. Our group previously explored psychiatric and somatic comorbidity among individuals with psychiatric diagnoses in Denmark at a broad level, aiming to highlight associations of interest and encouraging further, more detailed work on comorbidity for specific disorders.1

Aims of our study

This study adapted the methods of these comprehensive studies of psychiatric disorder comorbidity in the Danish population1,7 to parse comorbidity more extensively. We accessed Danish nationwide registers to provide sex-specific relative risks of diagnosis with a MC after ED diagnosis and vice versa. Additionally, we calculated bidirectional sex-specific measures of absolute risk between different types of EDs and MCs, and estimates for matched reference groups. We expected an increased risk of subsequent MC diagnoses among those diagnosed with EDs; and increased risk of subsequent ED diagnoses among those with prior MCs.

METHODS

To explore bidirectional associations between EDs and MCs, we determined: i) risk of a MC diagnosis after diagnosis with an ED (i.e., prior ED-later MC); and ii) risk of an ED diagnosis after diagnosis with a MC (i.e., prior MC-later ED). Although the analyses for both directions were similar, there are notable differences. The methods are described below, and with greater detail in the Online Material.

Study population and ascertainment of disorders of interest

This population-based cohort study included all individuals born in Denmark 1977- 2010 (N=2,127,404), identified in the Danish Civil Registration System. To be included in the analyses, individuals had to be residing in the country at the start of follow-up (described below).

Eating disorders

Unlike other psychiatric diagnoses, ED diagnoses are registered in both the Danish Psychiatric Central Research Register and the Danish National Patient Register; in 20-25% of AN cases, the first diagnosis is seen in the Patient Register. Both registers were used, which is an addition from previous studies. For each individual, the initial diagnosis date was ascertained for AN (ICD-8 code 306.50; ICD-10 F50.0 and F50.1), BN (ICD-10 F50.2 and F50.3), and EDNOS (ICD-8 306.58 and 306.59; ICD-10 F50.8 and F50.9). As a specific code did not exist for BN in ICD-8, it was not possible to consider BN in all analyses. We therefore combined BN and EDNOS diagnoses to create an Other Eating Disorders (OED) category consistent with previous investigations.8 Consequently, AN and OED were the primary ED categories of interest; when possible, we examined BN and EDNOS separately.

General medical conditions

We selected 12 MCs, consistent with previous work on somatic comorbidity and EDs (Table 1 and Supplementary Table S1).6 The following labels were derived to group MCs: neurological, infectious, immune, respiratory, gastrointestinal, skin, musculoskeletal, genitourinary, circulatory, endocrine, congenital, and injuries. Individuals with MCs were identified by combining information from the Danish National Patient Register and Cause of Death Register. MC diagnosis date was the date of the first relevant hospital diagnosis or, if the individual died from a MC without having received a previous diagnosis, date of death.

Table 1.

Eating disorders and general medical conditions: International Classification of Disease codes used for definition and the frequency of cases among all individuals born in Denmark between 1977-2010 (n=2,127,404)

Disorders Definition Number of cases Percentage
ICD-8 ICD-10
Eating Disorders
AN 306.50 F50.0, F50.1 9,492 0.4
OED 306.58, 306.59 F50.2, F50.3, F50.8, F50.9 13,366 0.6
BN - F50.2, F50.3 5,940 0.3
EDNOS 306.58, 306.59 F50.8, F50.9 9,015 0.4
General Medical Conditions
Neurologic 320-358 G00-G47, G60-G73, G91 119,398 5.6
Infectious 000-136 A00-B99 380,147 17.9
Immune D80-D89 6,271 0.3
Respiratory 460-466, 470-486, 490-493, 502-508, 783 J00-J46, R05-R06 646,925 30.4
Gastrointestinal 530-535, 540-542, 563, 570-577 K25-K37, K70-K85 138,047 6.5
Skin 680-698, 701, 708-709 L00-L54, L90-L95 214,699 10.1
Musculoskeletal 710-718 M00-M68 387,715 18.2
Genitourinary 580-584, 590, 592, 594, 601, 604 N00-N08, N10-N12, N20-N21, N41, N45 53,602 2.5
Circulatory 390-448, 450 I00-I79, I98.3 54,683 2.6
Endocrine 240-246, 250, 251-259 E00-E35 84,797 4.0
Congenital 740-759 Q00-Q99 250,716 11.8
Injury N800-N999, E807-E949, E960-E999 S00-T98, V01-X59, X85-Y98 1,933,287 90.9
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Study design

The main analyses examined the bidirectional associations between two EDs (AN and OED) and 12 MCs. We estimated associations between 46 temporally ordered ED-MC pairs (i.e., all possible pairs, except those for which congenital malformations would be the later disorder).

To provide estimates of relative risk for most pairs, follow-up started on 01/01/1983, or the individual’s sixth birthday, whichever occurred later (Supplementary Figure S1).

For prior ED-later GMs, depending on whether individuals had a diagnosis of a particular ED between 1983 (six years after the National Patient Register became available) and 2016, we estimated risk of receiving a diagnosis of each MC during follow-up. When considering chronic MCs (i.e., all except infections and injuries), individuals with a diagnosis prior to follow-up were excluded (“washed-out”).

For prior MC-later EDs, depending on whether individuals had a diagnosis of a particular MC between 1977 (when the National Patient Register started) and 2016, we estimated risk of receiving a diagnosis of each ED during follow-up. Individuals with an ED diagnosis prior follow-up were excluded. In addition to considering AN and OED when EDs were the later disorder, we explored BN and EDNOS separately.

The exceptions were when immune disorders were one of the disorders of interest (follow-up from 01/01/2000), as it was not possible to ascertain immune disorders prior to the use of ICD-10 in the registers. Further details are provided in the Supplement.

Statistical analysis

We compared the rate of diagnosis with a specific later disorder between those exposed and unexposed to each prior disorder using hazard ratios (HRs) and 95% confidence intervals (CIs), obtained via Cox proportional hazards models with age as the underlying time scale, using two models. Model A examined the association between a prior disorder and a later disorder, adjusted for sex and birthdate, which, in combination with underlying age in the models, also adjusted for calendar time. Model B included additional adjustment for other psychiatric disorders (detailed in the Supplementary Material)7 diagnosed before the prior disorder of interest. Prior OED were also included in Model B when AN was the ED of interest; when BN was the ED of interest, EDNOS were included. Individuals were followed up until the first of the following: diagnosis with the later disorder, death, emigration, or end of follow-up (31/12/2016). A hierarchy was applied to ED diagnoses: when considering OED or BN, AN also acted as a censoring event, like death or emigration. For EDNOS, both AN and BN acted as censoring events. Following the hierarchy AN, BN and EDNOS, ascribes association to a specific disorder not several.9

The prior disorders were treated as time-varying exposures for relative risks. Individuals were “unexposed” to the prior disorder, becoming “exposed” group when diagnosed for the first time with this disorder.

We also estimated the cumulative incidence proportion (CIP) of diagnosis with a later disorder after diagnosis of a prior disorder, using competing risks survival analyses to account for individuals’ simultaneous risk of the later disorder, dying, or emigrating. To compare CIPs among people with a prior disorder diagnosis to those among people without a diagnosis, a matched reference group was generated for each prior disorder. For every index person with the prior disorder, up to three age- and sex-matched individuals (who had not received a diagnosis of the relevant prior disorder at or before the age the index person was diagnosed) were randomly selected. More detailed information can be found in the Supplementary Appendix.

The Danish Data Protection Agency and the Danish Health Data Authority approved this study. By Danish law, no informed consent is required for a register based study using anonymised data.

RESULTS

In total, 2,127,404 million individuals were born in Denmark between 1977 and 2010. The number of cases of each MC and ED in this population is presented in Table 1, and their baseline characteristics are presented in Table S2 in the Supplement. The study population used to provide estimates of relative risk for all pairs except those including immune disorders, consisted of 2,063,912 Danish residents (1,005,347 females and 1,058,565 males), followed-up for 33.6 million person years. During this time, 9,433 individuals died and 43,264 emigrated. In the study population used for relative risks for pairs including immune disorders and for absolute risks, there were 2,058,865 million individuals (1,002,412 females and 1,056,453 males); however, total follow-up was 25.6 million person-years.

Bidirectional pairwise associations and absolute risks for all ED-MC pairs are shown in Fig 1, 2, 3 and Supplementary Figures S2–S10. General findings are described below.

Fig 1. The bidirectional associations between anorexia nervosa and general medical conditions.

Fig 1.

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The panels show the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between anorexia nervosa (AN) and general medical conditions (MCs) for all persons (men and women). Estimates were obtained via Cox proportional hazards models with age as the underlying time scale, adjusting for sex, calendar time and other mental disorders with onset before the prior disorder under study. In the left panel, the HRs show the risk of being diagnosed with a MC following a diagnosis of AN (i.e., AN is the prior disorder), compared to people without a diagnosis of AN. The right panel displays the HRs for the risk of being diagnosed with AN following an MC diagnosis (i.e., the MC of interest is the prior disorder), compared with people without the MC. The line of unity is shown as a blue dashed line in each plot.

Fig 2. The bidirectional associations between other eating disorders and general medical conditions.

Fig 2.

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The panels show the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between other eating disorders (OEDs) and general medical conditions (MCs) for all persons (men and women). Estimates were obtained via Cox proportional hazards models with age as the underlying time scale, adjusting for sex, calendar time and other mental disorders with onset before the prior disorder under study. In the left panel, the HRs show the risk of being diagnosed with a MC following a diagnosis of OED (i.e., OED is the prior disorder), compared with people without a diagnosis of OED. The right panel displays the HRs for the risk of being diagnosed with OED following an MC diagnosis (i.e., the MC of interest is the prior disorder), compared with people without the MC. The line of unity is shown as a blue dashed line in each plot.

Fig 3A and 3B. Absolute risks for general medical conditions and anorexia nervosa.

Fig 3A and 3B.

Fig 3A and 3B.

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Figure A shows estimates of absolute risks for a later diagnosis within a general medical condition (MC), following a diagnosis of anorexia nervosa (AN), for all persons. Figure B shows absolute risks for a later diagnosis of AN, following a diagnosis of an MC, for all persons. The cumulative incidence per 100 persons (solid lines for those with the prior disorder of interest, dashed lines for the matched reference groups) of receiving a diagnosis of each later disorder of interest, after a diagnosis of the prior disorder of interest. Shaded grey areas around the lines for those with the prior disorder of interest represent 95% confidence intervals (in some panels these are obscured by the estimates line). To aid readability, 95% confidence intervals are not shown for the reference groups (they are smaller than those for individuals with the disorder of interest). The horizontal axes show the time since first diagnosis of the prior disorder. The vertical axes show the cumulative incidence per 100 persons (and 95% CI). Note that vertical axes are not on the same scale for Figure A and Figure B.

NB. We did not calculate absolute risks for later congenital malformations.

Relative risks

Results adjusted for sex, birthdate, and other prior psychiatric disorders (i.e., Model B results) for all persons (both males and females) are shown for each direction for AN and OED in Fig 1 and 2. Results adjusted for sex and birthdate (Model A) can be found in the Supplementary Material.

Prior eating disorders-later medical conditions

Elevated risks for each later MC of interest were observed among all persons (i.e., both males and females combined) with the prior ED of interest (AN or OED), for 21 of 22 pairs; however, the 95% confidence interval (CI) included 1 for four of these. The point estimate for AN and subsequent immune disorders was slightly below one (0.94) but CIs were imprecise and included 1. The highest Model B HR was seen for prior AN and later circulatory disorders (2.05 [95% CI 1.86-2.27]). The lowest HR was 0.94 (95% CI 0.57-1.55), observed for AN and immune disorders. Model B estimates were slightly attenuated compared with Model A estimates (Supplementary Table S3). Sex-specific HRs can be seen in Supplementary Figures S2 and S3. The highest HR for males was for prior AN and later endocrine disorders (4.02 [95% CI 2.75-5.86]); for females it was for prior AN and subsequent circulatory disorders (1.99 [95% CI 1.79-2.21]).

Prior medical conditions-later eating disorders

For all persons, elevated risks for AN and OED were observed after diagnosis of all MCs of interest, and CIs did not include 1 for any pair, except immune disorders-OED. The highest HR was seen for prior circulatory disorders and later AN (1.98 [95% CI 1.71-2.28]). The lowest HR was for prior congenital disorders and subsequent AN (1.35 [95% CI 1.26-1.45]). All Model B estimates were slightly higher than their corresponding Model A estimate (Supplementary Table S4). Sex-specific HRs can be seen in Supplementary Figures S2 and S3. The highest HR for males was for prior immune disorders and later AN (4.96 [95% CI 1.59, 15.41]); for females it was for prior circulatory disorders and later AN (1.99 [95% CI 1.72-2.31]).

The HRs for BN and EDNOS excluding BN can be seen in Supplementary Figures S4 and S5. The risk was increased for those with each MC, with the 95% CIs of 22 of 24 HRs not including 1.

Absolute risks

Fig 3a shows the sex-specific absolute risk of receiving each MC diagnosis after a previous diagnosis of AN. Conversely, Fig 3b shows the risk of receiving an AN diagnosis after a prior diagnosis of each MC. Sex-specific absolute risks, as well as graphs for OED, BN and EDNOS as the later disorders of interest, are in the Supplementary Material.

Prior eating disorders-later MCs

For all pairs, cumulative incidence for all MCs was higher among those with prior EDs than without (with the exception of injuries). However, the proportions were similar. The highest cumulative incidence proportion (CIP) 15 years after an ED diagnosis was seen for AN-injuries (among those with AN 67.5% [95% CI 65.0-70.0%]). However, the CIP was even higher among their matched reference group (80.6% [95% CI 79.6-81.7%]); similarly, high CIPs were observed for OED-injuries.

Prior MCs-later eating disorders

For all pairs, cumulative incidence for EDs was higher among those with prior MCs than without. However, the proportions were similar. The highest CIP within 15 years after MC diagnosis for all persons was seen for endocrine disorders-AN, at 0.89% [95% CI 0.80, 1.01%]). For the matched reference group, the CIP reached 0.61% (95% CI 0.56, 0.66).

DISCUSSION

This population-based study, comprising 2.1 million individuals, shows patterns of comorbidity between EDs and MCs in both directions. In general, relative risks of being diagnosed with a range of MCs were higher among those with any type of ED, and, in a reciprocal fashion, risks of being diagnosed with any type of ED were higher among those with a range of MCs. Absolute risks for both later EDs and MCs among those with the prior disorders of interest were similar to risks in the reference groups, but at a slightly higher level.

Although our findings are in line with those in the broad studies of Momen et al. and Scott et al.1,3—which included prior EDs and later MCs—Tegethoff et al. found reduced risks for several MCs following EDs, including skin diseases, arthritis, heart disease and “any physical disease.”4 Furthermore, they found reduced risks for EDs following several MCs, including skin diseases, diabetes, and gastrointestinal diseases. However, Tegethoff et al. used survey data from to 13-18 year olds, so some differences could be due to the ages of their study population. A Swedish study looking at somatic comorbidity among those with binge-eating disorder (included in our EDNOS category) did not consider temporality of the diagnoses but found estimates of similar magnitude as in our study.6

Several studies have focused on single ED-MC pairs that have also highlighted ED comorbidity. For example, a study comparing patients hospitalized with BN with those hospitalized due to pregnancy complications10 found an increased risk of cardiovascular disease among those with BN; the observed HR was 4.25, which is higher than we found in our study. Another study reported that ED diagnoses were higher among Danish female adolescents hospitalized with infections, compared with those without hospitalizations for infections (HR of 1.22, similar in magnitude to our estimates of 1.58 for AN and 1.61 for OED in females).11 A recent review concluded that it is plausible that comorbidity between EDs and gastrointestinal diseases is common and this could occur in either direction, supporting our findings.12 Earlier studies have indicated associations between autoimmune diseases and EDs ;13,14 because of this link with some immune-mediated disorders, it could be expected that our study would have found risk of EDs to be higher in those with immune MCs, and vice versa. Although we found increased risks for most pairs of EDs and immune MCs, in both directions, the findings observed for prior AN-later immune MCs was suggestive of a slightly reduced risk, although 95% CIs included 1. It is important to note that immune disorders and auto-immune disorders comprise different disease entities. Additionally, for our immune MC category, 95% CIs are relatively wide; this is because they are not as common as some of the other MCs, and they are the only MC that could not be identified using ICD-8 codes.

Estimates of relative risk were attenuated when adjusting for additional prior psychiatric and EDs for the direction of prior EDs -later MCs, which is in keeping with evidence linking psychiatric disorders with an increased risk of subsequent MCs. However, for the direction of prior MCs-later EDs , adjustment for prior psychiatric disorders increased the resulting HRs slightly. It may be that prior MCs have stronger associations with EDs when no other psychiatric disorders are present, but this is speculative.

We had expected that HRs for MCs among people with AN would be slightly higher than HRs for MCs among people with OED (compared with their respective reference groups), as physical complications from AN are typically more severe.15 Although higher HRs were seen for AN for several MCs, this was not true for all MCs, and generally magnitudes did not differ greatly. A previous study in Danish adolescents found that risks for autoimmune and autoinflammatory diseases were elevated in those with EDs compared to those without;13 the risk was elevated to a greater extent among those with BN than those with AN. Additionally, the patterns observed may reflect the higher mortality rates seen in those with AN; a higher proportion of those with AN may die before the ages at which MCs are typically diagnosed.16,17

Risk factors for AN do differ considerably from risk factors for other psychiatric disorders, for example some early adversities are associated with a decreased risk of AN, while there were increased risks for BN and EDNOS, and further increased risks for other psychiatric disorders).9 Additionally, associations for parental ages and multiple births have been shown to vary for different types of EDs .18 Further, in comparison to other psychiatric disorders, AN has more a pronounced metabolic component at a genetic level.19 However, when it comes to somatic comorbidities, EDs are similar, and do not differ appreciably from other psychiatric disorders.1

When considering absolute risks, we found higher proportions of those with EDs went on to be diagnosed with MCs, and higher proportions of those with MCs to be subsequently diagnosed with EDs . However, despite cumulative incidence being slightly higher following diagnosis with each disorder of interest, levels generally reflected those in the respective reference groups. The exception to this was later injuries, which were higher in the reference groups for both prior AN and OED. Although the risk of certain injuries could be expected to be higher among individuals who have previously had AN (e.g., fractures due to the effects of AN on bone mineral density, which can be evident after just one year of AN),20,21 the observed lower risk could be due to behavioural differences, particularly in the earlier years post-diagnosis. Alternatively, it could be related to personality differences; a previous study suggested that people with EDs show higher levels of harm avoidance and lower levels of novelty-seeking (although the study was limited to women),22 which may result in them engaging in fewer behaviors that could lead to injury. By the end of the first year after start of follow-up, 12 out of 100 individuals with AN and 20 out of 100 in the reference group had attended hospital with an injury. Relatively speaking, cumulative incidence of injuries was almost 60% higher among those in the reference group than those in the AN group after the first year of follow-up. However, at 15 years post follow-up, 73 out of 100 individuals with AN and 78 out of 100 in the reference group had attended hospital with an injury; so after 15 years, cumulative incidence of injuries was only 6% higher in the reference group.

The associations found were not markedly different depending on direction. There may be a number of reasons for the associations observed. Although in some cases, associations may be causal; for others, there may be shared mechanisms, or environmental or genetic risk factors. Alternatively, once receiving treatment for one disorder, other symptoms may be identified, leading to subsequent referrals and diagnoses.23

Strengths and limitations

Our register-based study has several strengths. It uses the nationwide registers of Denmark, which provide data on the whole population, yielding a large sample size and minimizing selection bias. Danish citizens have free and equal access to health care, thus any effect related to the ability to afford private insurance/access to health care is reduced. It is mandatory in Denmark for all hospitals to report discharge diagnoses to central registries. The study is not susceptible to recall bias and self-reporting bias (limitations of cross-sectional surveys which rely on retrospective recall in those individuals alive at the time of the survey and willing to participate). We considered all types of EDs , included a comprehensive range of MCs, and provided estimates of relative and absolute risks.

There are important limitations that should also be considered. First, in our study we included only 12 types of MCs. However, the MCs selected were considered to be particularly relevant comorbidities for people with EDs . Furthermore, our analyses comprised individual pairs of EDs and MCs, which does not reflect the full complexity of comorbidity as patients may experience multiple MCs, as well as multiple EDs over time. Second, there may be misclassification with regard to ascertainment of conditions. Validity may vary across diagnoses. We do not have data on those who do not seek treatment for their disorders or those treated entirely in primary care settings. NICE highlights that EDs are often untreated, especially in men.24 Furthermore, prescription medications were not used to ascertain MCs. Although this will affect ascertainment of some MCs more than others, cases will be biased to the more severe end of the clinical spectrum. As an example, people who present with hypertension or dyslipidemia, which are often managed in primary care with medication, may be misclassified as not having a circulatory MC. Whereas it is difficult to speculate regarding the effect on HRs, underestimation of CIPs is likely, among both those with prior disorders and their reference groups. Misclassification can also occur for onset: the date of administrative onset, as recorded in the registers, will be later than the actual onset of EDs and many MCs. A German study reported that the mean duration of untreated AN was over two years, in which time physiological effects could have already occurred.25 This may lead to incorrect temporal ordering of EDs and MCs. Third, the length of follow-up is limited by the period of time the relevant registers have been available, as well as the ICD codes in use at different times. When looking at absolute risks for prior EDs-later MCs, MCs had to be diagnosed within 15 years of the ED diagnosis (due to data availability); this duration of follow-up may have been insufficient for the population to experience late onset MC diagnosis (and thus to capture all potential comorbidity). Studies on psychiatric disorders have suggested that risk of comorbid diagnoses is greatest in the years succeeding the index diagnosis,1,7,10 but longer follow-up, which can be incorporated into future studies as more register data become available, will be informative. Fourth, there are likely to be several factors associated with both EDs and MCs that we were unable to consider in our study, such as socioeconomic status, genetic factors, or childhood adversity. Finally, the generalizability of our findings outside of Denmark may be limited. Observed patterns of comorbidity may vary in other countries, especially those with different health care structures.

There are several ways that research can add to our understanding of comorbidity in those with different types of ED. Future studies can further investigate associations at the broad level, for example, by considering patterns of comorbidity or causes of mortality. In addition, studies can evaluate associations in finer detail, by considering individual pairs of EDs and MCs, and the specific diagnoses within each category.

This study provides a broad examination of the comorbidity between different types of EDs and MCs, presenting relative risks and absolute risks of the associations in both directions. To our knowledge, it is the most comprehensive examination of comorbidity between EDs and general MCs. Our findings highlight that those with EDs have increased risks of most types of MCs, and those with MCs have increased risks of EDs – risks are elevated bidirectionally. This information may be useful in clinical settings, particularly for clinicians working with patients with ED diagnoses, to help early identification of MCs, as most MCs appear to be more common for individuals with EDs. However, while there were some differences in risk by ED type, magnitudes did not differ greatly for AN versus other types of EDs .

Supplementary Material

Suppl

FUNDING

ZY acknowledges grant support from NIMH (R01MH105500; R01MH120170) and Brain and Behavior Research Foundation (NARSAD Young Investigator Award, grant # 28799). CMB is supported by NIMH (R01MH120170; R01MH119084; R01MH118278; U01 MH109528); Brain and Behavior Research Foundation Distinguished Investigator Grant; Swedish Research Council (Vetenskapsrådet, award: 538-2013-8864); Lundbeck Foundation (Grant no. R276-2018-4581). JM is supported by the Danish National Research Foundation (Niels Bohr Professorship). JM is employed by The Queensland Centre for Mental Health Research which receives core funding from the Department of Health, Queensland Government. OPR has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 837180. LVP received funding from Lundbeck Foundation (Grant no. R276-2018-4581) and The Novo Nordisk Foundation (Grant no. NNF20OC0064993). The investigators conducted the research independently. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

DECLARATION OF INTERESTS

CM Bulik reports: Shire (grant recipient, Scientific Advisory Board member); Idorsia (consultant); Pearson (author, royalty recipient). The other authors have nothing to disclose.

Contributor Information

Natalie C. Momen, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.

Oleguer Plana-Ripoll, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark.

Cynthia M. Bulik, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

John McGrath, National Centre for Register-based Research, Aarhus BSS, Aarhus University, 8210 Aarhus V, Denmark; Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Queensland, Australia.

Laura M. Thornton, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Zeynep Yilmaz, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Department of Psychiatry, University of North Carolina at Chapel Hill, NC, Chapel Hill, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Liselotte Vogdrup Petersen, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.

DATA AVAILABILITY

No additional data available. Access to individual-level Denmark data is governed by Danish authorities. These include the Danish Data Protection Agency, the Danish Health Data Authority, the Ethical Committee, and Statistics Denmark. Each scientific project must be approved before initiation, and approval is granted to a specific Danish research institution. Researchers at Danish research institutions may obtain the relevant approval and data. International researchers may gain data access if governed by a Danish research institution having needed approval and data access.

REFERENCES

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

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NIHMS1952236-supplement-Suppl.docx (3.2MB, docx)

Data Availability Statement

No additional data available. Access to individual-level Denmark data is governed by Danish authorities. These include the Danish Data Protection Agency, the Danish Health Data Authority, the Ethical Committee, and Statistics Denmark. Each scientific project must be approved before initiation, and approval is granted to a specific Danish research institution. Researchers at Danish research institutions may obtain the relevant approval and data. International researchers may gain data access if governed by a Danish research institution having needed approval and data access.

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