Research suggests that economic declines contribute to mortality risks from suicide and drug poisoning, but how the economy impacts individuals’ risks of these deaths has been challenging to specify. ...Building on recent theoretical advances, we investigate how adolescent occupational expectations and preparation contribute to suicide and drug poisoning deaths in a shifting economy. We use High School and Beyond data linked to adult mortality records for men that were exposed to a decline in labor market share and wages in predominantly blue-collar occupations during early adulthood. We find that adolescent men who expected these occupations had increased risks of suicide and drug poisoning death as adults net of educational and occupational attainment in early adulthood. Family background and occupational preparation are risk factors for death by drug poisoning but not suicide. Our findings improve our understanding of how labor market uncertainty shapes individuals’ vulnerability to suicide and drug poisoning death.
Deaths from self-injury are increasing. Understanding the sources of risk is important for prevention and treatment.
To estimate the risks of suicide and drug poisoning deaths among adult men whose ...adolescent occupational expectations were not met in adulthood.
This cohort study included a sample of men interviewed as part of the High School and Beyond study, a nationally representative study of US high school sophomores and seniors in 1980, who were interviewed every 2 years through 1986; those who were sophomores in 1980 were reinterviewed in 1992. Men who survived to 1992 and reported occupational expectations were included in the present study. Death records prior to 2018 were linked to mortality databases and released in 2019. Data analysis was conducted from May to October 2020.
Occupational expectations.
Survival or death by suicide, drug poisoning, chronic liver disease, heart disease, cancer, or some other cause, categorized from International Classification of Diseases, Ninth Revision and Tenth Revision codes. Competing risk Fine-Gray survival models regressed cause of death on adolescent occupational expectations and covariates.
The 11 680 men in the High School and Beyond cohort study had a median (interquartile range) age of 29 (28-30) years in 1992, when the analysis of their future mortality began. Most men survived until 2015 (11 060 weighted percentage, 95.0%). Reported causes of death were suicide (60 weighted percentage, 0.5%), drug poisoning (40 weighted percentage, 0.4%), chronic liver disease (20 weighted percentage, 0.2%), heart disease (130 weighted percentage, 1.0%), cancer (100 weighted percentage, 1.0%), and other (280 weighted percentage, 2.0%). Subhazard ratios for death by suicide and drug poisoning were 2.91 (95% CI, 1.07-7.88; P = .04) and 2.62 (95% CI, 1.15-5.94; P = .02) times higher, respectively, among those who in 1980 expected to hold a subbaccalaureate occupation that later declined in labor market share compared with those with professional occupational expectations. The actual job held by men did not attenuate the hazards of deaths from suicide and drug poisoning.
In this cohort study, men whose occupational expectations were not met because of labor market declines were at a higher risk of death from suicide or drug poisoning than men with different occupational expectations. Interventions to mitigate labor market changes should account for individuals' expectational ideals.
Biallelic variants in the ERCC excision repair 6 like 2 gene (ERCC6L2) are known to cause bone marrow failure (BMF) due to defects in DNA repair and mitochondrial function. Here, we report on eight ...cases of BMF from five families harboring biallelic variants in ERCC6L2, two of whom present with myelodysplasia. We confirm that ERCC6L2 patients’ lymphoblastoid cell lines (LCLs) are hypersensitive to DNA-damaging agents that specifically activate the transcription coupled nucleotide excision repair (TCNER) pathway. Interestingly, patients’ LCLs are also hypersensitive to transcription inhibitors that interfere with RNA polymerase II (RNA Pol II) and display an abnormal delay in transcription recovery. Using affinity-based mass spectrometry we found that ERCC6L2 interacts with DNA-dependent protein kinase (DNA-PK), a regulatory component of the RNA Pol II transcription complex. Chromatin immunoprecipitation PCR studies revealed ERCC6L2 occupancy on gene bodies along with RNA Pol II and DNA-PK. Patients’ LCLs fail to terminate transcript elongation accurately upon DNA damage and display a significant increase in nuclear DNA–RNA hybrids (R loops). Collectively, we conclude that ERCC6L2 is involved in regulating RNA Pol II-mediated transcription via its interaction with DNA-PK to resolve R loops and minimize transcription-associated genome instability. The inherited BMF syndrome caused by biallelic variants in ERCC6L2 can be considered as a primary transcription deficiency rather than a DNA repair defect.
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