People with schizophrenia included in biobanks may be less severely affected
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Key takeaways:
- UK Biobank participants with schizophrenia had genotypes indicative of less severe disease vs. clinically recruited participants.
- UK Biobank participants also had higher education levels and employment rates.
Volunteer-based biobanks can provide insight into people with less severe forms of illnesses like schizophrenia compared with samples recruited from clinical settings, according to a study published in JAMA Psychiatry.
“Millions of participants across the world from newly available biobanks will be made available for research within the next 5 years,” Sophie E. Legge, PhD, a research associate in the division of psychological medicine and clinical neurosciences at Cardiff University School of Medicine in the United Kingdom, and colleagues wrote. “However, these samples are known to be subject to ascertainment biases, in particular healthy volunteer bias.”
They continued, “For example, of the 9.2 million people invited to participate in the UK Biobank, the 5.5% that participated are disproportionately female, socioeconomically advantaged and white. They are also less likely to be obese or to smoke, report fewer health conditions and have lower mortality rates.”
To determine how individuals with schizophrenia included in biobanks compare with patients from clinical research settings to inform future research, Legge and colleagues compared genotypic features among people with schizophrenia through polygenic risk scores (PRS) and rates of copy number variation (CNV), as well as phenotypic features.
The cross-sectional study included 1,438 people with schizophrenia (38.2% women; mean age, 54.7 years; standard deviation [SD], 8.3 years) from the UK Biobank and 4,758 people (28.9% women; mean age, 38.2 years; SD, 8.1 years) recruited from clinical settings. These included CLOZUK, a sample of patients diagnosed with treatment-resistant schizophrenia taking clozapine; and the CardiffCOGS, Cardiff F-Series and Cardiff Affected Sib-Pairs patient cohorts, the latter of which also included people with schizoaffective disorder if one sibling had schizophrenia.
Researchers also compared those with schizophrenia with 499,475 UK Biobank control individuals (54.4% women; mean age, 56.5 years; SD, 8.1 years) without any mental or behavioral disorders.
Individuals with schizophrenia from the UK Biobank had a strong genetic correlation with the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study data (rg = 0.98; standard error, 0.18). The UK Biobank schizophrenia PRS explained 6.8% of the variance in liability.
When looking at genotypic features, the PRS of UK Biobank participants was significantly lower than participants from CLOZUK, Cardiff F-Series and Cardiff Affected Sib-Pairs. UK Biobank participants’ CNV rate also was significantly lower than participants in CLOZUK (1.6% vs. 2.7%; OR = 0.6; 95% CI, 0.35-0.95). UK Biobank participants had a lower CNV rate than participants in CardiffCOGS, Cardiff F-Series and Cardiff Affected Sib-Pairs combined, but it was not statistically significant.
Researchers also noticed a difference in phenotypic features between UK Biobank participants and participants recruited from clinical settings. UK Biobank participants showed patterns associated with lower severity of illness, including lower rates of smoking and a lower likelihood to be male. Also, male participants were more likely to have children; however, there was no difference among female participants. In addition, UK Biobank participants had higher education levels, employment rates and an older average age of psychosis onset.
Compared with the control population, those with schizophrenia in the UK Biobank were more likely to be male and less likely to be married or have children, and they had less education and more comorbid conditions like epilepsy and heart disease.
“Individuals with schizophrenia in UK Biobank have genomic and phenotypic features consistent with expectations for those with a diagnosis of schizophrenia but represent those less severely affected,” researchers wrote. “The inclusion of such cases in wider schizophrenia studies has the potential to enhance representation of the full spectrum of illness severity.”