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. 2023 Jan 12;6(3):e202201673.
doi: 10.26508/lsa.202201673. Print 2023 Mar.

Secondary findings in a large Pakistani cohort tested with whole genome sequencing

Aliaksandr Skrahin  1 , Huma Arshad Cheema  2 , Maqbool Hussain  3 , Nuzhat Noureen Rana  4 , Khalil Ur Rehman  5 , Raman Kumar  6 , Gabriela Oprea  7 , Najim Ameziane  7 , Arndt Rolfs  7   8 , Volha Skrahina  7
Affiliations

Secondary findings in a large Pakistani cohort tested with whole genome sequencing

Aliaksandr Skrahin et al. Life Sci Alliance. .

Abstract

Studies on genomic secondary findings (SFs) are diverse in participants' characteristics, sequencing methods, and versions of the ACMG SF list. Based on whole genome sequencing and the version 3.1 of the ACMG SF list, we studied SFs in 863 individuals from five different regions in Pakistan. We identified 24 ACMG SFs in 23 (2.7%) of 863 individuals: 18 of 24 were related to cardiovascular disease and four to cancer syndromes. In addition to ACMG SFs, we identified 16 (1.9%) participants with pathogenic and likely pathogenic variants in genes that were not related to the participants' clinical conditions but with clear medical actionability (non-ACMG SFs): 4 of 16 were related to eye diseases, two to metabolic disorders, and two to urinary system disorders. By testing a large Pakistani cohort with whole genome sequencing, we concluded that in countries such as Pakistan, the ACMG SF list could be expanded, and our non-ACMG SF list is one example.

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Conflict of interest statement

A Skrahin, A Rolfs, G Oprea, N Ameziane, and V Skrahina declared employment in genomic testing company; HA Cheema, M Hussain, NN Rana, KU Rehman, and R Kumar did not declare any competing interest related to this study.

Figures

Figure 1.
Figure 1.. The ACMG v3.1 secondary findings.
Disease categories and related gene-disease pairs. The ACMG, the American College of Medical Genetics and Genomics; DCM, dilated cardiomyopathy; LQTS, long QT syndrome; FH, familial hypercholesterolemia; ARVC, arrhythmogenic right ventricular cardiomyopathy; HBC, hereditary breast cancer; HBOC, hereditary breast and ovarian cancer; MH, malignant hyperthermia.
Figure 2.
Figure 2.. Non-ACMG secondary finding.
Disease categories and related gene-disease pairs. The ACMG, the American College of Medical Genetics and Genomics; ARMD, age-related macular degeneration type 2; SD, Stargardt disease type 1; PCD, primary ciliary dyskinesia type 3; FRS, Fanconi renotubular syndrome type 2; VMD, vitelliform macular dystrophy type 4; CCHS, congenital central hypoventilation syndrome type 2; SSE, sitosterolemia type 1; PHOU, primary hyperoxaluria type 1; NS, nephrotic syndrome; type 9; RGU, renal glucosuria; FTAA, familial thoracic aortic aneurysm type 9; TDMG, thyroid dyshormonogenesis type 5; vWD, von Willebrand disease type 1; AHUS, atypical hemolytic uremic syndrome type 6; EBD, epidermolysis bullosa dystrophica.
Figure 3.
Figure 3.. The ACMG secondary findings and primary findings.
Frequency of (gene)-disease pairs. The ACMG, the American College of Medical Genetics and Genomics; BTD, biotinidase deficiency; WD, Wilson disease; PD, Pompe disease; DCM, dilated cardiomyopathy; RB, retinoblastoma; PJS, Peutz-Jeghers syndrome; LS, Lynch syndrome; HBOC, hereditary breast and ovarian cancer; MS, Marfan syndrome; FH, familial hypercholesterolemia; HCM, hypertrophic cardiomyopathy; MH, malignant hyperthermia; HBC, hereditary breast cancer; ARVC, arrhythmogenic right ventricular cardiomyopathy; LQTS, long QT syndrome.
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