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The Lancet. Psychiatry Sep 2021Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in...
BACKGROUND
Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.
METHODS
We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.
FINDINGS
4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.
INTERPRETATION
This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.
FUNDING
Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Attention Deficit Disorder with Hyperactivity; Female; Humans; Membrane Glycoproteins; Middle Aged; Phenotype; Receptors, Interleukin-1; Registries; Risk Factors; Sweden; Young Adult
PubMed: 34242595
DOI: 10.1016/S2215-0366(21)00171-1 -
Twin Research and Human Genetics : the... Oct 2016The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has...
The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has not been hitherto examined. Prior twin studies have varied with regard to the detection of shared environmental effects and sex differences in the etiology of AUD. In this report, structural equation modeling in OpenMx was applied to (1) the three types of alcohol registration in a population-based sample of male-male twins and reared-together full and half siblings (total 208,810 pairs), and (2) AUD, as a single diagnosis, in male-male, female-female, and opposite-sex (OS) twins and reared-together full and half siblings (total 787,916 pairs). An independent pathway model fit best to the three forms of registration and indicated that between 70% and 92% of the genetic and 63% and 98% of the shared environmental effects were shared in common with the remainder unique to each form of AUD registration. Criminal registration had the largest proportion of unique genetic and environmental factors. The best fit model for AUD estimated the heritability to be 22% and 57%, respectively, in females and males. Both shared (12% vs. 6%) and special twin environment (29% vs. 2%) were substantially more important in females versus males. In conclusion, AUD ascertained from medical, pharmacy, and criminal Swedish registries largely share the same genetic and environmental risk factors. Large sex differences in the etiology of AUD were seen in this sample, with substantially stronger familial environmental and weaker genetic effects in females versus males.
Topics: Adult; Aged; Alcohol-Induced Disorders; Female; Humans; Male; Middle Aged; Models, Genetic; Registries; Risk Factors; Siblings; Twins
PubMed: 27515133
DOI: 10.1017/thg.2016.62 -
Child Neurology Open 2022Distal 7q11.23 deletions are variably associated with epilepsy, intellectual disability and neurobehavioural abnormalities. The relative importance of different genes...
Distal 7q11.23 deletions are variably associated with epilepsy, intellectual disability and neurobehavioural abnormalities. The relative importance of different genes in this region in contributing to different phenotypes is not clear, though and are both thought to play important roles. We performed thorough phenotyping on members of a family in which multiple members carried a relatively small 0.8 Mb distal 7q11.23 deletion, affecting 17 genes. Two brothers and a half-brother had all inherited the 7q11.23 deletion from their mother. The eldest two both had global developmental impairment and genetic generalized epilepsy, involving absence, myoclonic or myoclonic-atonic seizures. There was no history of seizures in the mother or her youngest son, but both also had developmental impairment. Distal 7q11.23 deletions affecting and may cause developmental impairment and genetic generalized epilepsy, with considerable intrafamilial phenotypic variability.
PubMed: 35481155
DOI: 10.1177/2329048X221093173 -
Acta Obstetricia Et Gynecologica... Oct 2023Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now... (Observational Study)
Observational Study
INTRODUCTION
Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now accumulating evidence that pregnancy-related pelvic girdle pain originates from the sacroiliac joints and the pubic symphysis as well as their extra-articular ligaments. However, the heritability of the disease remains to be determined. We hypothesized that there is an increased familial risk of pregnancy-related pelvic girdle pain.
MATERIAL AND METHODS
A population-based national database linkage registry study of approximately 9.3 million individuals within 4.2 million families in Sweden with a recruitment period from 1997 to 2018. The Swedish Multi-generation register was used to find female pairs of twins, full siblings, half-siblings and first cousins where both in the pairs had a completed pregnancy. The outcome measure was diagnosis of pregnancy-related pelvic girdle pain (International Classification of Diseases-10 O26.7 [1997-2018]) in the first pregnancy. Data was obtained from the Swedish Hospital Discharge Register, the Swedish Outpatient Care Register, the Swedish Medical Birth Register, the Primary Healthcare Register, and Medical Treatment Register. Cox regression analysis was used to calculate adjusted estimated effect of the exposure variable familial history of pregnancy-related pelvic girdle pain on the outcome variable pregnancy-related pelvic girdle pain at first birth.
RESULTS
From the registers, 1 010 064 women pregnant with their first child within 795 654 families were collected. In total, 109 147 women were diagnosed with pregnancy-related pelvic girdle pain. The adjusted hazard ratio for a familial risk of pregnancy-related pelvic girdle pain was 2.09 (95% CI 1.85-2.37) among twins (monozygotic and dizygotic), 1.78 (95% CI 1.74-1.82) in full siblings, 1.16 (95% CI 1.06-1.28) in half-siblings from the mother, 1.09 (95% CI 1.024-1.16) in half-siblings from the father and 1.09 (95% CI 1.07-1.12) in first cousins.
CONCLUSIONS
This nationwide observational study showed a familial clustering of pregnancy-related pelvic girdle pain. The hazard ratio for the condition was associated with the degree of relatedness, suggesting that heredity factors contribute to the development of pregnancy-related pelvic girdle pain. There is no causal treatment available for pregnancy-related pelvic girdle pain and further studies are now encouraged to clarify the specific genetic factors that contribute to the disease and for future targeted interventions.
Topics: Female; Humans; Pregnancy; Family; Genetic Predisposition to Disease; Heredity; Pelvic Girdle Pain; Pregnancy Complications; Sweden
PubMed: 37470484
DOI: 10.1111/aogs.14646 -
Was Cinderella just a fairy tale? Survival differences between stepchildren and their half-siblings.Philosophical Transactions of the Royal... Jun 2021The death of a parent, particularly the mother, is linked to a suite of negative outcomes across the life-course. Compounding concerns for child outcomes are...
The death of a parent, particularly the mother, is linked to a suite of negative outcomes across the life-course. Compounding concerns for child outcomes are expectations of poor treatment by step-parents after parental remarriage. Indeed, folk tales of step-parental abuse abound cross-culturally and are embedded into stories taught to children. To understand why child outcomes might be sensitive to levels of relatedness within the household, evolutionary-oriented research targets patterning in parental expenditure in ways predicted to maximize inclusive fitness. In particular, parents are expected to prioritize investments in their biological children. However, stepfamilies are only formed after children experience multiple unfortunate events (e.g. parental loss, poverty), blurring causal interpretations between step-parental presence and stepchild outcomes. Moreover, stepchildren have been shown to be integral to household functioning, caring for their half-siblings and stabilizing relationships. These results challenge narrow views of adaptive behaviour; specifically, that step-parents, unlike biological parents, do no stand to reap fitness benefits from the care that they provide to their stepchildren. To evaluate these critiques, we analyse the survival outcomes of stepchildren. We include over 400 000 individuals from across a natural fertility period (1847-1940) in the United States state of Utah and examine the consequences of parental loss and step-parental introduction. Our analyses yield three key results: (i) exposure to maternal loss in childhood is associated with elevated mortality risk, (ii) parental remarriage does not increase the risk of mortality among stepchildren compared to non-stepchildren who too had lost a parent, and (iii) stepchildren enjoy higher survival than their half-siblings within the same family. Ultimately, this work contributes to the increasingly recognized importance of cooperative relationships among non-kin for childcare and household functioning. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.
Topics: Adolescent; Child; Child, Preschool; Family Characteristics; Fathers; Female; Humans; Infant; Male; Marriage; Mortality; Mothers; Siblings; Social Support; Utah
PubMed: 33938278
DOI: 10.1098/rstb.2020.0032 -
Psychological Medicine May 2019Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic...
BACKGROUND
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
METHODS
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
RESULTS
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
CONCLUSIONS
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Topics: Adult; Alcoholism; Anorexia Nervosa; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bipolar Disorder; Case-Control Studies; Cohort Studies; Depressive Disorder, Major; Family; Female; Gene-Environment Interaction; Genotype; Humans; Male; Mental Disorders; Obsessive-Compulsive Disorder; Quantitative Trait, Heritable; Schizophrenia; Schizophrenic Psychology; Siblings; Sweden
PubMed: 30221610
DOI: 10.1017/S0033291718002039 -
International Journal of Epidemiology Jun 2020Early puberty is a risk indicator for adult diseases. Identification of modifiable causes of earlier puberty is, therefore, warranted. We estimate the association...
BACKGROUND
Early puberty is a risk indicator for adult diseases. Identification of modifiable causes of earlier puberty is, therefore, warranted. We estimate the association between childhood body mass index (BMI) and pubertal timing in a cohort study and in a sibling-matched study to adjust for unobserved time-stable confounders shared within families.
METHODS
For the cohort study, 11 046 of 22 439 (49%) invited children, born 2000-203, from the Danish National Birth Cohort (DNBC) had information on childhood BMI at 7 years and self-reported, half-yearly puberty information from 11 years on Tanner stages, menarche, voice break, first ejaculation, acne, and axillary hair. For the sibling-matched study, 1700 brothers and sisters were included among 86 820 live-born singletons from the DNBC.
RESULTS
Childhood overweight (85th ≤ BMI < 95th percentile) and obesity (BMI ≥ 95th percentile) were associated with earlier age attaining the pubertal milestones in a dose-dependent manner in boys and girls. When modelling all pubertal milestones simultaneously, the pubertal milestones were attained earlier in: overweight boys: -3.1 [95% confidence interval (CI): -4.5, -1.7] months, overweight girls: -5.5 (95% CI: -7.1, -3.9) months, obese boys: -3.5 (95% CI: -5.1, -2.0) months, obese girls: -5.2 (95% CI: -7.1, -3.4) months compared with normal weight (BMI < 85th percentile) children. In the sibling-matched study, higher BMI was associated with earlier age at attaining most pubertal milestones in girls, but only a tendency toward earlier pubertal timing was observed in boys.
CONCLUSIONS
Childhood overweight and obesity were associated with earlier pubertal timing even after adjustment for unobserved time-stable confounders shared within families.
Topics: Child; Cohort Studies; Denmark; Female; Humans; Male; Pediatric Obesity; Puberty; Siblings; Time Factors
PubMed: 32372073
DOI: 10.1093/ije/dyaa056 -
Genes Feb 2024Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study,...
Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (A) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.
Topics: Humans; DNA Fingerprinting; High-Throughput Nucleotide Sequencing; Gene Frequency; Polymorphism, Single Nucleotide; Scandinavians and Nordic People
PubMed: 38397213
DOI: 10.3390/genes15020224 -
Developmental Medicine and Child... Oct 2022To describe use of health services, unmet needs relating to health services, and identify factors associated with service use among adults with cerebral palsy (CP) in...
AIM
To describe use of health services, unmet needs relating to health services, and identify factors associated with service use among adults with cerebral palsy (CP) in Ireland.
METHOD
Data relating to demographics, secondary diagnoses, current use of health services and assistive devices, and unmet needs for both were obtained on adults with CP from the National Physical and Sensory Disability Database. Logistic regression was used to identify factors associated with service use.
RESULTS
A total of 1268 adults with CP were included in this study. Over half were male (56%) and 78% lived with parents, siblings, or other family relatives. Physiotherapy, occupational therapy, and orthotics/prosthetic services were the most commonly used services, used by 57%, 48%, and 35% of the sample respectively. Unmet needs were highest for physiotherapy (23%) and occupational therapy services (13%). Age, sex, living arrangements, and wheelchair use were frequently associated with current service use.
INTERPRETATION
Adults with CP used a wide range of health services and unmet needs were reported for all services. The findings highlight a need for planning and development of services to meet their needs, regardless of their age, mobility level, or living arrangements.
WHAT THIS PAPER ADDS
Adults with cerebral palsy (CP) in Ireland used a wide range of therapeutic, respite, personal assistance, and support services. Unmet needs were highest for physiotherapy and occupational therapy services. Adults aged 25 years and above were less likely to use therapy services compared with younger adults. Adults living with parents, siblings, or family relatives were less likely to use personal assistance and physiotherapy services.
Topics: Adult; Cerebral Palsy; Female; Health Services; Health Services Needs and Demand; Humans; Ireland; Male; Physical Therapy Modalities
PubMed: 35396701
DOI: 10.1111/dmcn.15233 -
Nature Aug 2023Social anthropology and ethnographic studies have described kinship systems and networks of contact and exchange in extant populations. However, for prehistoric...
Social anthropology and ethnographic studies have described kinship systems and networks of contact and exchange in extant populations. However, for prehistoric societies, these systems can be studied only indirectly from biological and cultural remains. Stable isotope data, sex and age at death can provide insights into the demographic structure of a burial community and identify local versus non-local childhood signatures, archaeogenetic data can reconstruct the biological relationships between individuals, which enables the reconstruction of pedigrees, and combined evidence informs on kinship practices and residence patterns in prehistoric societies. Here we report ancient DNA, strontium isotope and contextual data from more than 100 individuals from the site Gurgy 'les Noisats' (France), dated to the western European Neolithic around 4850-4500 BC. We find that this burial community was genetically connected by two main pedigrees, spanning seven generations, that were patrilocal and patrilineal, with evidence for female exogamy and exchange with genetically close neighbouring groups. The microdemographic structure of individuals linked and unlinked to the pedigrees reveals additional information about the social structure, living conditions and site occupation. The absence of half-siblings and the high number of adult full siblings suggest that there were stable health conditions and a supportive social network, facilitating high fertility and low mortality. Age-structure differences and strontium isotope results by generation indicate that the site was used for just a few decades, providing new insights into shifting sedentary farming practices during the European Neolithic.
Topics: Adult; Child; Female; Humans; Male; Agriculture; Anthropology, Cultural; Burial; Fathers; Fertility; France; History, Ancient; Mortality; Pedigree; Siblings; Social Support; Strontium Isotopes; Social Environment; Mothers
PubMed: 37495691
DOI: 10.1038/s41586-023-06350-8