Most illnesses are a combination of symptoms. We should look at the symptoms one at a time

My heading above is a simplified version of the heading below. And I agree in principle with the propositon it expressees. And the conclusion they draw from their survey data supports that proposition.

But it doesn't! The correlations they report are abysmally low so the findings actually DISPROVE what they set out to show

And that happens all the time in medical research. I have documented it many times. What amazes me is that such crazy studies regularly get reported in top medical journals, as they did below. I am glad that I have lived to 80 so that I can continue to point such follies out -- as there is clearly an acute shorage of sanity about the matters concerned.

The sad thing is that Google has search-blocked me so that my critical comments will only ever become known to regular readers of this blog. A Google search of the subject will not disclose these comments. Criticism is essential to science but Google don't seem to care about that

UPDATE: Google appears to have lifted the search block on this blog. Things I write here will now appear in response to a searches for information on topics I have written about here. So my comments above should appear soon in searches


Polygenic Scores and Networks of Psychopathology Symptoms

Giulia G Piazza et al.

Abstract

Importance
Studies on polygenic risk for psychiatric traits commonly use a disorder-level approach to phenotyping, implicitly considering disorders as homogeneous constructs; however, symptom heterogeneity is ubiquitous, with many possible combinations of symptoms falling under the same disorder umbrella. Focusing on individual symptoms may shed light on the role of polygenic risk in psychopathology.

Objective
To determine whether polygenic scores are associated with all symptoms of psychiatric disorders or with a subset of indicators and whether polygenic scores are associated with comorbid phenotypes via specific sets of relevant symptoms.

Design, Setting, and Participants
Data from 2 population-based cohort studies were used in this cross-sectional study. Data from children in the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the primary analysis, and data from children in the Twins Early Development Study (TEDS) were included in confirmatory analyses. Data analysis was conducted from October 2021 to January 2024. Pregnant women based in the Southwest of England due to deliver in 1991 to 1992 were recruited in ALSPAC. Twins born in 1994 to 1996 were recruited in TEDS from population-based records. Participants with available genetic data and whose mothers completed the Short Mood and Feelings Questionnaire and the Strength and Difficulties Questionnaire when children were 11 years of age were included.

Main Outcomes and Measures
Psychopathology relevant symptoms, such as hyperactivity, prosociality, depression, anxiety, and peer and conduct problems at age 11 years. Psychological networks were constructed including individual symptoms and polygenic scores for depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), body mass index (BMI), and educational attainment in ALSPAC. Following a preregistered confirmatory analysis, network models were cross-validated in TEDS. Results Included were 5521 participants from ALSPAC (mean [SD] age, 11.8 [0.14] years; 2777 [50.3%] female) and 4625 participants from TEDS (mean [SD] age, 11.27 [0.69] years; 2460 [53.2%] female). Polygenic scores were preferentially associated with restricted subsets of core symptoms and indirectly associated with other, more distal symptoms of psychopathology (network edges ranged between r = −0.074 and r = 0.073). Psychiatric polygenic scores were associated with specific cross-disorder symptoms, and nonpsychiatric polygenic scores were associated with a variety of indicators across disorders, suggesting a potential contribution of nonpsychiatric traits to comorbidity. For example, the polygenic score for ADHD was associated with a core ADHD symptom, being easily distracted ( r = 0.07), and the polygenic score for BMI was associated with symptoms across disorders, including being bullied ( r = 0.053) and not thinking things out ( r = 0.041).

Conclusions and Relevance
Genetic associations observed at the disorder level may hide symptom-level heterogeneity. A symptom-level approach may enable a better understanding of the role of polygenic risk in shaping psychopathology and comorbidity.

June 2024 JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2024.1403

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