Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups:...

Area of Science:

• Cardiovascular Genetics
• Medical Genomics
• Population Health

Background:

• Hypertrophic cardiomyopathy (HCM) affects diverse populations, necessitating ethnicity-specific genetic insights.
• The Cardiac Inherited Diseases Registry New Zealand (CIDRNZ) provides a platform to study HCM genetics in Aotearoa/New Zealand's multiethnic cohort.
• Understanding genetic variant prevalence across ethnicities is crucial for equitable diagnostic strategies.

Purpose of the Study:

• To characterize HCM probands in New Zealand by ethnicity and genetic variant status.
• To determine the yield of clinical genetic testing for HCM across different ethnic groups.
• To analyze the spectrum of pathogenic/likely pathogenic (P/LP) variants in relation to self-identified ethnicity.

Main Methods:

• Analysis of clinical data, family history, and genetic test results from 336 HCM probands in the CIDRNZ over 17 years.
• Categorization of probands by self-identified ethnicity (European, Māori, Pacific, other).
• Assessment of P/LP variant detection rates and variant types stratified by ethnicity, sex, and clinical presentation.

Main Results:

• A pathogenic or likely pathogenic (P/LP) genetic variant was identified in 40% of all HCM probands.
• P/LP variant detection was lower in Māori or Pacific probands (27%) compared to European or other ethnicities (43%).
• Variant-positive probands were younger at diagnosis and more likely to have experienced sudden cardiac events.

Conclusions:

• P/LP variants in HCM are associated with earlier disease onset and increased risk of sudden cardiac events.
• Ethnic disparities exist in P/LP variant identification for HCM, with lower rates observed in Māori and Pacific populations.
• Targeted genetic testing strategies may be needed to address ethnic variations in HCM genetic diagnoses.