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JAMA May 2014Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental...
IMPORTANCE
Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved.
OBJECTIVE
To provide estimates of familial aggregation and heritability of ASD.
DESIGN, SETTING, AND PARTICIPANTS
A population-based cohort including 2,049,973 Swedish children born 1982 through 2006. We identified 37,570 twin pairs, 2,642,064 full sibling pairs, 432,281 maternal and 445,531 paternal half sibling pairs, and 5,799,875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained.
MAIN OUTCOMES AND MEASURES
The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors.
RESULTS
In the sample, 14,516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100,000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude.We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64).
CONCLUSIONS AND RELEVANCE
Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.
Topics: Adolescent; Adult; Autistic Disorder; Child; Child, Preschool; Cohort Studies; Female; Genetic Predisposition to Disease; Humans; Male; Maternal Age; Paternal Age; Registries; Risk; Sweden; Twins, Monozygotic; Young Adult
PubMed: 24794370
DOI: 10.1001/jama.2014.4144 -
JAMA Jun 2018Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of...
IMPORTANCE
Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear.
OBJECTIVE
To determine whether there is an association between stress-related disorders and subsequent autoimmune disease.
DESIGN, SETTING, AND PARTICIPANTS
Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients.
EXPOSURES
Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions.
MAIN OUTCOMES AND MEASURES
Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.
RESULTS
The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively; P for interaction < .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ≤179, 180-319, and ≥320 days, respectively; P for trend = .03).
CONCLUSIONS AND RELEVANCE
In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.
Topics: Adult; Autoimmune Diseases; Female; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Registries; Retrospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Siblings; Socioeconomic Factors; Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic; Stress, Psychological; Sweden
PubMed: 29922828
DOI: 10.1001/jama.2018.7028 -
Translational Psychiatry Feb 2023Individuals with autism spectrum disorder (ASD), in addition to the core features of the disease, experience a higher burden of co-occurring medical conditions. This...
Individuals with autism spectrum disorder (ASD), in addition to the core features of the disease, experience a higher burden of co-occurring medical conditions. This study sought to describe the frequency and distribution of comorbidit conditions in individuals with ASD, and systematically evaluate the possibility that pre- and postnatal exposures (e.g., preterm birth, hypoxia at birth, traumatic brain injury, and fetal alcohol syndrome) associated with ASD may also be linked with distinct comorbidities. We used the SPARK study database, launched by the Simons Foundation Autism Research Initiative (SFARI). Comorbidities considered in the study included neurological, cognitive, psychiatric, and physical conditions. The study sample consisted of 42,569 individuals with ASD and their 11,389 non-ASD siblings (full and half siblings). Majority (74%) of individuals with ASD had at least one comorbidity, and had a greater average number of comorbidities than their non-ASD siblings. Preterm birth and hypoxia at birth were the most common peri-natal exposures in the sample. In logistic regression models adjusted for covariates, these exposures were associated with several distinct comorbidities in ASD cases, including attention and behavior problems, psychiatric and neurological disorders, and growth conditions. A similar pattern of association was also observed in non-ASD siblings. Our findings underscore that individuals with ASD experience a greater burden of comorbidities, which could be partly attributable to the higher rates of perinatal exposures compared to their non-ASD siblings. Study findings, if replicated in other samples, can inform the etiology of comorbidity in ASD.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Autism Spectrum Disorder; Premature Birth; Comorbidity; Autistic Disorder; Siblings
PubMed: 36841830
DOI: 10.1038/s41398-023-02374-w -
Fa Yi Xue Za Zhi Apr 2019Objective To evaluate the effectiveness of single nucleotide polymorphism (SNP) genoty-ping in combination with identity by state (IBS) strategy in full sibling...
Objective To evaluate the effectiveness of single nucleotide polymorphism (SNP) genoty-ping in combination with identity by state (IBS) strategy in full sibling testing. Methods Thirty-five blood samples were collected from a four-generation family. Ninety autosomal SNPs were genotyped using Precision ID Identity Panel. The distribution of IBS scores for full siblings and other relationships were calculated and compared. The relationships were determined using Fisher discriminant function and threshold method, respectively. Results Based on family members and previous research, 44, 30, 111, 71 and 1 000 pairs of full siblings (FS), grandparent-grandchild (GG), uncle/aunt-nephew/niece (UN), first cousins (FC) and unrelated individuals (UI) were obtained, respectively. The average IBS scores were 148, 130, 132, 124 and 120, respectively. Except for the GG and UN pairs, the distribution differences among the other relationships had statistical significance (<0.05). The false rates of Fisher discriminant function to determine relationships were 1.3%, 22.3%, 17.0% and 38.7% for FS, GG, UN and FC, respectively. Based on the simulation data, the thresholds =128 and =141 were recommended to determine full sibling relationships (the false rate ≤0.05%). Conclusion The 90 SNP genetic markers included in the Precision ID Identity Panel meet the testing requirements for full sibling relationships. The threshold method based on IBS has a relatively lower false rate and is more flexible.
Topics: Genotype; Genotyping Techniques; Humans; Polymorphism, Single Nucleotide; Siblings
PubMed: 31135116
DOI: 10.12116/j.issn.1004-5619.2019.02.014 -
Genetics, Selection, Evolution : GSE Apr 2023The construction of covariance matrices that account for the genetic relationships among individuals, using pedigree or genotype data, is integral to genetic...
The construction of covariance matrices that account for the genetic relationships among individuals, using pedigree or genotype data, is integral to genetic evaluations, which are now routinely used in the field of animal breeding. The objective of the present study was to estimate the standard deviation in the proportion of the segregating genome that is shared between pairs of full-sibling cattle and sheep independently. Post edits, genotype data comprising 46,069 autosomal single nucleotide polymorphisms (SNPs) were available for 4532 unique full-sibling sheep pairs, as well as for their respective parents. Post edits, genotypes from 50,493 autosomal SNPs were also available for 10,000 unique full-sibling cattle pairs, as well as their respective parents. Genomic relationship matrices were constructed for the sheep and cattle populations, separately. After accounting for both parental genomic inbreeding and the genomic relationship between both parents, the standard deviation in full-sibling cattle and sheep genomic relationships was 0.040 and 0.037 units, respectively. In addition, the intercept value from a linear regression model which regressed each full-sibling genomic relationship on both sire and dam inbreeding, as well as the genomic relationship between the parents, was 0.499 (0.001) for sheep and 0.500 (0.001) for cattle, conforming to the expectation that full-siblings, on average, share 50% of their segregating genome.
Topics: Cattle; Animals; Sheep; Humans; Siblings; Genome; Genotype; Inbreeding; Genomics; Pedigree; Polymorphism, Single Nucleotide
PubMed: 37072693
DOI: 10.1186/s12711-023-00802-5 -
BMC Medicine Sep 2023Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery.
METHODS
A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis.
RESULTS
Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study.
CONCLUSIONS
Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.
Topics: Female; Pregnancy; Humans; Siblings; Cesarean Section; Delivery, Obstetric; Asthma; Outcome Assessment, Health Care
PubMed: 37679672
DOI: 10.1186/s12916-023-03030-2 -
Journal of Family Issues May 2022Using the National Longitudinal Study of Adolescent to Adult Health ( = 1,366), we examine how major life course statuses are related to sibling relationships during...
Using the National Longitudinal Study of Adolescent to Adult Health ( = 1,366), we examine how major life course statuses are related to sibling relationships during emerging adulthood with attention to similarities and differences in these statuses between sibling dyads. We find that full-time employment, marriage/cohabitation, and parenthood are related to more distant sibling relationships, whereas college education is related to closer sibling relationships. Similarities in employment between the siblings are related to closer relationships, but differences in education, marriage/cohabitation, and parenthood are related to closer relationships, in that respondents report more help-seeking and emotional closeness with their siblings who have higher education than theirs; unpartnered respondents report more calls and fewer fights with their partnered siblings; and childless respondents report more visits and emotional closeness with their parenting siblings. Examining both one's and one's sibling's life course statuses is important in understanding life course variations in sibling relationships.
PubMed: 36438182
DOI: 10.1177/0192513x211022401 -
Fa Yi Xue Za Zhi Dec 2016To explore the identification method of full sibling between two males with microdeletion and mutation of Y chromosome.
OBJECTIVES
To explore the identification method of full sibling between two males with microdeletion and mutation of Y chromosome.
METHODS
DNA were extracted from two samples. The type testing of Y-STR and autosomal STR were performed. Full sibling between two individuals was calculated by IBS, ITO and discriminant functions methods.
RESULTS
There were 2 loci mutations existed in 33 Y-STR loci and one of the two samples had 19 loci deletions. The IBS of two samples was 53 and greater than the threshold which was 42; FSI was 1.36×10¹⁶ and far greater than 19. The discriminant function of full sibling-unrelated individual was greater than , which meant the two individuals tend to be full sibling.
CONCLUSIONS
The methods of IBS, ITO and discriminant functions of full sibling-unrelated individual can be used comprehensively to provide more reliable expert opinion in microdeletion and mutation of Y chromosome in full sibling identification.
Topics: Alleles; Chromosome Aberrations; Chromosomes, Human, Y; Discriminant Analysis; Forensic Genetics; Humans; Male; Polymerase Chain Reaction; Sequence Deletion; Siblings
PubMed: 29205972
DOI: 10.3969/j.issn.1004-5619.2016.06.011 -
BMJ Open May 2021The number and rank order of siblings could be of importance for risk of cardiovascular disease and mortality. Previous studies have used only fatal events for risk...
BACKGROUND
The number and rank order of siblings could be of importance for risk of cardiovascular disease and mortality. Previous studies have used only fatal events for risk prediction. We, therefore, aimed to use also non-fatal coronary and cardiovascular events in fully adjusted models.
METHODS
From the Multiple-Generation Register in Sweden, data were used from 1.36 million men and 1.32 million women (born 1932-1960), aged 30-58 years at baseline and with follow-up from 1990 to 2015. Mean age at follow-up was 67 years (range 55-83 years). Fatal and non-fatal events were retrieved from national registers.
RESULTS
Compared with men with no siblings, those with 1-2 siblings had a lower, and those with four or more siblings had a higher adjusted risk of cardiovascular events. Again, compared with men with no siblings, those with more than one sibling had a lower total mortality risk, and those with three or more siblings had an increased risk of coronary events.Correspondingly, compared with women with no siblings those women with three siblings or more had an increased risk of cardiovascular events, and those with two siblings or more had an increased risk of coronary events. Women with one sibling or more were at lower total mortality risk, following full adjustment.
CONCLUSION
Being first born is associated with a favourable effect on non-fatal cardiovascular and coronary events for both men and women. The underlying biological mechanisms for this should be studied in a sociocultural context.
Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Female; Heart; Humans; Male; Middle Aged; Risk Factors; Siblings; Sweden
PubMed: 34035122
DOI: 10.1136/bmjopen-2020-042881 -
Circulation. Genomic and Precision... Apr 2023Complete atrioventricular block (CAVB) is a major reason for implantation of permanent pacemakers, but knowledge of CAVB inheritance is sparse. This nationwide study...
BACKGROUND
Complete atrioventricular block (CAVB) is a major reason for implantation of permanent pacemakers, but knowledge of CAVB inheritance is sparse. This nationwide study aimed to determine the occurrence of CAVB in first-, second-, and third-degree relatives (full siblings, half-siblings, and cousins).
METHODS
The Swedish multigeneration register was linked to the Swedish nationwide patient register for the period 1997 to 2012. All Swedish full sibling, half-sibling, and cousin pairs born to Swedish parents between 1932 and 2012 were included. Competing risks and time-to-event, subdistributional hazard ratios (SHRs) according to Fine and Gray and hazard ratios using Cox proportional hazards model were estimated using robust SEs and considering the relatedness of relatives (full siblings, half-siblings, cousins). Additionally, odds ratios (ORs) for CAVB were calculated for traditional cardiovascular comorbidities.
RESULTS
The study population (N=6 113 761) consisted of 5 382 928 full siblings, 1 266 391 half-siblings, and 3 750 913 cousins. In total, 6442 (0.11%) unique individuals were diagnosed with CAVB. Of these, 4200 (65.2%) were males. SHRs for CAVB were 2.91 for full siblings (95% CI, 2.43-3.49), 1.51 for half-siblings (0.56-4.10), and 3.54 for cousins (1.73-7.26) of affected individuals. Age-stratified analysis showed higher risk in young individuals born from 1947 to 1986: SHR, 5.30 (3.78-7.43) for full siblings, SHR, 3.30 (1.06-10.31) for half-siblings, and SHR, 3.15 (1.39-7.17) for cousins. Similar familial HRs according to Cox proportional hazard model and ORs were obtained without any major differences. Apart from familial relationship, CAVB was associated with hypertension (OR, 1.83), diabetes (OR, 1.41), coronary heart disease (OR, 2.08), heart failure (OR, 5.01), and structural heart disease (OR, 4.59).
CONCLUSIONS
Risk of CAVB among relatives of affected individuals depends on relationship degree, being strongest in young siblings. The familial association extending to third-degree relatives indicates presence of genetic components in the cause of CAVB.
Topics: Male; Humans; Female; Sweden; Atrioventricular Block; Family; Siblings; Parents
PubMed: 36802810
DOI: 10.1161/CIRCGEN.121.003654