Implications of comorbidity and ascertainment bias for identifying disease genes

Area of Science:

• Medical Genetics
• Psychiatry
• Biostatistics

Background:

• Comorbidity, the co-occurrence of disorders, is observed at higher rates in clinical samples than population-based samples.
• This difference is often attributed to individuals with multiple conditions being more likely to seek medical care.

Purpose of the Study:

• To define and explain "spurious comorbidity" and "spurious comorbidity bias."
• To demonstrate how this bias can affect genetic association studies, particularly family-based designs.
• To highlight the implications for genetic research in neuropsychiatric disorders.

Main Methods:

• Conceptual explanation of ascertainment bias and its impact on comorbidity.
• Theoretical demonstration of spurious comorbidity bias in family-based association studies.

Main Results:

• Spurious comorbidity arises from ascertainment bias, where seeking care for one condition increases the likelihood of diagnosing a comorbid one.
• Spurious comorbidity bias can lead to incorrect associations between genetic loci and phenotypes.
• This bias can significantly skew conclusions in genetic association studies.

Conclusions:

• Ascertainment bias is a critical factor to consider in genetic studies, especially for complex traits like neuropsychiatric disorders.
• The phenomenon of spurious comorbidity bias may contribute to the challenges in replicating findings in psychiatric genetics.
• Researchers must account for ascertainment bias to ensure the validity of genetic association studies.