Do Biobank Recall Studies Matter? Long-Term Follow-Up of Research Participants With Familial Hypercholesterolemia

Miriam Nurm; Anu Reigo; Margit Nõukas; Liis Leitsalu; Tiit Nikopensius; Marili Palover; Tarmo Annilo; Maris Alver; Aet Saar; Toomas Marandi; Tiia Ainla; Andres Metspalu; Tõnu Esko; Neeme Tõnisson

doi:10.3389/fgene.2022.936131

Do Biobank Recall Studies Matter? Long-Term Follow-Up of Research Participants With Familial Hypercholesterolemia

Front Genet. 2022 Jul 19:13:936131. doi: 10.3389/fgene.2022.936131. eCollection 2022.

Authors

Miriam Nurm^{1

2}, Anu Reigo¹, Margit Nõukas^{1

3}, Liis Leitsalu¹, Tiit Nikopensius¹, Marili Palover^{1

3}, Tarmo Annilo¹, Maris Alver^{1

4}, Aet Saar^{5

6}, Toomas Marandi^{5

6}, Tiia Ainla^{5

6}, Andres Metspalu^{1

3}, Tõnu Esko¹, Neeme Tõnisson^{1

7}

Affiliations

¹ Institute of Genomics, University of Tartu, Tartu, Estonia.
² Institute of Technology, University of Tartu, Tartu, Estonia.
³ Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁴ Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
⁵ Department of Cardiology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
⁶ Cardiology Centre, North Estonia Medical Centre, Tallinn, Estonia.
⁷ Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.

Abstract

Recall-by-genotype (RbG) studies conducted with population-based biobank data remain urgently needed, and follow-up RbG studies, which add substance to this research approach, remain solitary. In such studies, potentially disease-related genotypes are identified and individuals with those genotypes are recalled for consultation to gather more detailed clinical phenotypic information and explain to them the meaning of their genetic findings. Familial hypercholesterolemia (FH) is among the most common autosomal-dominant single-gene disorders, with a global prevalence of 1 in 500 (Nordestgaard et al., Eur. Heart J., 2013, 34 (45), 3478-3490). Untreated FH leads to lifelong elevated LDL cholesterol levels, which can cause ischemic heart disease, with potentially fatal consequences at a relatively early age. In most cases, the pathogenesis of FH is based on a defect in one of three LDL receptor-related genes-APOB, LDLR, and PCSK9. We present our first long-term follow-up RbG study of FH, conducted within the Estonian Biobank (34 recalled participants from a pilot RbG study and 291 controls harboring the same APOB, LDLR, and PCSK9 variants that were included in the pilot study). The participants' electronic health record data (FH-related diagnoses, lipid-lowering treatment prescriptions) and pharmacogenomic risk of developing statin-induced myopathy were assessed. A survey was administered to recalled participants to discern the impact of the knowledge of their genetic findings on their lives 4-6 years later. Significant differences in FH diagnoses and lipid-lowering treatment prescriptions were found between the recalled participants and controls (34 and 291 participants respectively). Our study highlights the need for more consistent lipid-lowering treatment adherence checkups and encourage more follow-up RbG studies to be performed.

Keywords: biobank to practice; familial hypercholesterolemia (FH); lipid lowering treatment; long-term survey; participant survey; pharmacogenomic risk assessment; recall-by-genotype.