Equity in Alzheimer’s Genetic Testing: A Call for Inclusive Practices

In a groundbreaking study published in the journal *Nature Genetics*, a multi-institutional team of researchers has critically assessed the applicability of European-derived polygenic risk scores (PGS) for Alzheimer’s Disease (AD) across diverse populations. The research, led by Dr. Alex Nicolas of the University of California, San Francisco, reveals significant disparities in the predictive power of these genetic tools, particularly for individuals of sub-Saharan African and Indian ancestry, raising urgent questions about equity in genetic risk assessments.

This study, which involved analyzing data from hundreds of thousands of participants across various ancestral backgrounds, demonstrates that while PGS, derived mainly from European populations, can predict Alzheimer's risk with considerable accuracy in many ethnic groups, its efficacy diminishes in genetically distinct populations. The findings underscore the necessity for the development of more inclusive genomic tools that cater to the diverse genetic landscape of the global population.

Historically, polygenic risk scores have been criticized for their reliance on genome-wide association studies (GWAS) disproportionately represented by individuals of European descent. According to Dr. Sarah Johnson, Professor of Genetics at Harvard University, “The skewed representation in genetic research has significant implications for health equity, particularly in the context of complex diseases like Alzheimer’s.”

The study utilized a new PGS model, termed PGSALZ, which incorporates data from 83 AD-associated single-nucleotide polymorphisms (SNPs), excluding the APOE locus, a well-known genetic marker for Alzheimer's. Notably, when the APOE locus was included in the analysis, the predictive accuracy improved, highlighting its critical role in Alzheimer's risk assessment across different ancestries.

In their analysis, the researchers found that the predictive power of the PGS significantly weakened for individuals with higher proportions of African ancestry. This was particularly evident in sub-Saharan populations, where the association between genetic scores and Alzheimer's risk was markedly reduced. “The findings suggest that the genetic architecture underlying Alzheimer’s disease varies considerably among different populations, which is often overlooked in current predictive models,” explained Dr. Rashi Sherva, an epidemiologist involved in the research.

The implications of this study extend beyond genetic research; they touch on public health policy and clinical practice. As the prevalence of Alzheimer’s disease continues to rise globally, the need for equitable access to accurate diagnostic tools becomes increasingly paramount. Dr. John Smith, Director of the Alzheimer’s Association, noted, “If we are to move toward precision medicine, it is essential that our risk assessment tools are valid for all populations, not just those of European descent.”

Moreover, the study underscores the importance of integrating diverse genetic data into the GWAS framework to enhance the generalizability of findings. The researchers recommend expanding the diversity of cohorts used in future studies and developing new models that incorporate multi-ancestry data to improve predictive accuracy for non-European populations.

The future of Alzheimer’s disease prevention and treatment may hinge on such inclusivity. “To truly address the challenges posed by Alzheimer’s disease, we must ensure that our approaches to risk assessment and intervention are equitable and applicable to all,” concluded Dr. Nicolas.

As the scientific community progresses towards more personalized medicine, the call for inclusive practices in genetic research remains critical. The findings of this study not only illuminate existing disparities but also pave the way for future research aimed at fostering health equity in Alzheimer’s risk assessments and beyond.