Б
том ХXXI, 2025, № 2
ДРУЖЕСТВО
НА КАРДИОЛОЗИТЕ
В БЪЛГАРИЯ
РЕДАКЦИОНЕН КОМЕНТАР
EDITORIAL
doi: 10.3897/bgca dio.31.e173631
In oduc ion o pe sona-
lised genomics
Genomics is among he
as es -e ol ing scien i i c
disciplines. A he beginning
o his cen u y he i s d a
o he human genome was
published – a miles one ha
anks among he g ea es
scien i i c achie emen s o
ou ime. Rapid echnologi-
cal ad ances since hen ha e made sequencing much
as e , mo e p ecise and a mo e aff o dable, culmina -
ing in he comple e, gapless, elome e- o- elome e as-
sembly o he human genome ( epo ed in 2021) ha
e ealed p e iously inaccessible DNA egions. O e
he pas wo decades p ecision genomics has d ama i-
cally expanded ou unde s anding o genome a chi ec-
u e and gene unc ion, which in u n has powe ed he
ise o pe sonalised medicine: an app oach ha ailo s
diagnos ic and he apeu ic s a egies o he unique
cha ac e is ics o each pa ien , including hei gene ic
makeup and o he bioma ke s. Mo ing beyond he a-
di ional “one-size- i s-all” model, pe sonalised medicine
s a i i es pa ien s in o subg oups using genomic da a,
molecula p o i ling and compu a ional ools o diagnose
condi ions ea lie , p edic disease isk mo e accu a ely,
and selec he apies ha a e mo e likely o wo k o
a gi en indi idual. When combined wi h ad ances in
a i i cial in elligence and high- h oughpu molecula as-
says, genomics p omises mo e p ecise, eff ec i e and
pa ien -cen ed heal hca e – and he i eld o ca diology
s ands o bene i pa icula ly. Gene ic in o ma ion now
enables de i ni i e diagnosis o inhe i ed hea disease,
e i nes popula ion-le el isk s a i i ca ion, and helps se-
lec sa e , mo e eff ec i e he apies. As whole-genome
app oaches, polygenic modelling and high- i deli y long-
ead sequencing mo e om “p omising” o p ac ical
ools, clinicians can inc easingly pe sonalise p e en-
ion, diagnosis and ea men ac oss he spec um o
ca dio ascula disease.
Monogenic diagnosis: cla i y whe e i ma e s
mos
A clea clinical implica ion o p ecision genomics
in ca diology is he diagnosis o monogenic diso de s.
Pa hogenic a ian s in single genes unde lie many in-
he i ed channelopa hies and a hy hmias ( o example
long-QT and sho -QT synd omes, B ugada synd ome),
ca diomyopa hies (hype ophic, dila ed, a hy hmogenic
and me abolic o ms), ao opa hies, amilial dyslipidae-
mias, and ce ain h ombophilias and clo ing diso de s.
Es ablishing a gene ic diagnosis p o ides immedia e clin-
ical alue: i con i ms ae iology, enables cascade ( amily)
es ing, in o ms p ognosis (some geno ypes p edic ap-
id p og ession o high a hy hmic isk) and guides man-
agemen decisions such as de ice implan a ion, a ge ed
he apies o pe sonalised p ophylaxis. In some cases,
pa hogenic a ian s ac oss wo o mo e genes join ly
cause ca diac disease, e l ec ing digenic o oligogenic
inhe i ance. Such complex mechanisms o pa hogenesis
unde line he need o es mul iple genes o iden i y he
exac causa i e a ian s. As he ca alogue o disease-as-
socia ed genes has con inued o expand o e ecen
decades, clinical es ing p og essed om a ge ed gene
panels o whole-exome sequencing (WES), which cap-
u es all p o ein-coding genes, and now o whole-genome
sequencing (WGS). WGS in e oga es he en i e genome
and inc eases diagnos ic yield beyond panels and WES
by de ec ing deep-in onic o o he non-coding ( egula o-
y) a ian s as well as s uc u al a ian s (dele ions, du-
plica ions, in e sions and complex ea angemen s) ha
we e p e iously missed, imp o ing diagnos ic a es in se-
lec ed pa ien s wi h unexplained ca dio ascula disease.
Rapid WGS has demons a ed clinical u ili y in acu e
se ings ( o example c i ically ill neona es and selec ed
ca diac p esen a ions), sho ening he diagnos ic odyssey
and in o ming u gen managemen . Genome-wide analy-
sis o en gene a es a la ge numbe o a ian s o unce -
ain signi i cance (VUS), which o en equi e amily es ing
o de e mine inhe i ance pa e ns and aid in eclassi ying
hem as likely pa hogenic o likely benign.
Polygenic isk: s a i ying common disease
ea lie
Al hough mos a e ca diac diseases a e mono-
genic (o occasionally digenic), many common ca dio-
ascula complica ions such as s oke o myoca dial
in a c ion a e polygenic, a ising om he combined in-
l uence o nume ous gene ic a ian s oge he wi h li e-
s yle and en i onmen al ac o s. Each indi idual ca ies
a unique balance o p o ec i e gene ic a ian s and isk
alleles, each con ibu ing o o e all liabili y. Bios a is i-
cal app oaches such as polygenic isk sco es (PRS)
es ima e his inhe i ed isk and suppo popula ion-le el
GENOMICS IN THE ERA OF PERSONALISED PRECISION MEDICINE
GENOMICS IN THE ERA OF PERSONALISED PRECISION MEDICINE
ГЕНОМИКА В ЕРАТА НА ПЕРСОНАЛИЗИРАНАТА ПРЕЦИЗНА МЕДИЦИНА
ГЕНОМИКА В ЕРАТА НА ПЕРСОНАЛИЗИРАНАТА ПРЕЦИЗНА МЕДИЦИНА
L. Balabanski. Genomics in he e a o pe sonalised p ecision medicine
6
s a i i ca ion. PRS agg ega e he small eff ec s o many
common a ian s in o a single nume ic measu e o ge-
ne ic suscep ibili y compa ed o he common popula-
ion. Fo condi ions like co ona y a e y disease and
a ial i b illa ion, polygenic sco es can iden i y indi id-
uals wi h subs an ially ele a ed isk. In some s udies,
hose in he highes PRS pe cen iles ace se e al- old
g ea e isk han he a e age pe son. Such indi iduals
may bene i om ea lie li es yle op imisa ion, pe son-
alised p ophylaxis, imaging su eillance, o pha ma-
cop e en ion. A limi a ion is ha mos ea ly PRS algo-
i hms we e de i ed om Eu opean coho s, and hei
p edic i e accu acy declines when applied o o he
non-Eu opean ances ies. Recen mul i-ances y mod-
els ha e imp o ed ans e abili y, bu pe o mance s ill
a ies ac oss popula ions, making local alida ion es-
sen ial be o e clinical use.
Pha macogenomics: sa e , mo e eff ec i e
p esc ibing
Gene ics is al eady changing how we p esc ibe
ca dio ascula d ugs. Well- alida ed gene–d ug pai s
( o example CYP2C19 geno ype and clopidog el e -
i cacy, o SLCO1B1 and s a in-associa ed myopa hy
isk) ha e e idence-based implemen a ion guidelines
om pha macogenomics conso ia. Geno ype-guided
an ipla ele selec ion a e pe cu aneous co ona y in-
e en ion (PCI), and geno ype-in o med s a in choice
o dosing, a e p ac ical examples o p ecision p esc ib-
ing ha educe ad e se e en s and imp o e ou comes
o indi idual pa ien s. Inco po a ing pha macogene ic
es ing in o ou ine clinical wo k l ows – ei he ahead o
ea men o a he poin o p esc ibing – is a sensible
and p agma ic nex s ep o ca diology.
Long- ead sequencing: p o iding new insigh s
abou he genome
Genome-wide clinical es ing app oaches (WES/
WGS) in he las 20 yea s ha e elied mos ly on sho -
ead nex -gene a ion sequencing echnologies. While
highly accu a e and cos -eff ec i e, sho eads ypically
span only ~100-150 base pai s a a ime, which makes
i diffi cul o esol e epe i i e egions, de ec la ge
s uc u al a ian s, o iden i y o he complex ch omo-
somal ea angemen s. These limi a ions lea e gaps in
ou abili y o ully cha ac e ise he genome, pa icula -
ly in egions ha a e clinically ele an bu diffi cul o
sequence. Long- ead sequencing echnologies – ex-
empli i ed by Ox o d Nanopo e and Paci i c Bioscienc-
es (PacBio) HiFi pla o ms – ha e ecen ly s a ed o
o e come many o hese challenges. Long eads can
span epea s and s uc u al a ian s, enable phasing o
alleles, and di ec ly e eal epigene ic me hyla ion pa -
e ns as well, subs an ially inc easing diagnos ic yield.
PacBio’s HiFi eads combine long ead leng h wi h e y
high pe -base accu acy, while Ox o d Nanopo e p o-
ides na i e DNA sequencing in eal- ime, and po able
sequencing capabili ies. Toge he , hese app oaches
enhance de ec ion o pa hogenic s uc u al a ian s
and allow cha ac e isa ion o genomic egions ha
we e p e iously in ac able. As cos s decline and anal-
ysis pipelines ma u e, hyb id s a egies ha combine
sho - and long- ead da a a e poised o become a s an-
da d componen o clinical genomics, off e ing mo e
comp ehensi e and accu a e diagnos ics o ca dio-
ascula and o he gene ic diseases. These echniques
will be pa icula ly aluable in pa ien s who emain un-
diagnosed a e con en ional es ing.
Ba ie s, esponsibili ies and he pa h o
ou ine use
Despi e i s g ea p omise, in eg a ing genomics in o
ou ine ca diology equi es ca e ul a en ion o se e -
al challenges. Va ian in e p e a ion some imes yields
esul s o unce ain signi i cance ha equi e addi ional
es ing o eanalysis. Polygenic isk sco es o com-
mon diseases mus be in e p e ed cau iously and a e
s ongly in l uenced by ances y. Many aspec s o clini-
cal genomics s ill need s anda disa ion, including bioin-
o ma ic pipelines, da a s o age, in o med consen , and
he epo ing o inciden al i ndings. Clinicians also e-
qui e aining o in e p e and communica e gene ic e-
sul s eff ec i ely o pa ien s. Finally, cos -eff ec i eness
and eimbu semen policies will in l uence adop ion and
accessibili y. Add essing hese issues demands mul i-
disciplina y collabo a ion among ca diologis s, clinical
gene icis s, bioin o ma icians, e hicis s, and heal hca e
policymake s.
Conclusion: a p agma ic op imism
Pe sonalised genomics has laid he ounda ion o
p ecision medicine. O e he pas decade, gene ics and
clinical ca e ha e con e ged in ema kable ways: wha
once belonged p ima ily o esea ch labo a o ies is now
inc easingly eshaping pa ien managemen in e e yday
ca diology. Genomics is nei he a panacea no a eplace-
men o clinical judgemen . Ra he , i off e s a powe ul
pe spec i e o unde s anding he molecula ae iology o
ca dio ascula disease, enhancing diagnos ic accu a-
cy, pe sonalising isk assessmen , and e i ning he apy.
As genomic echnologies become as e , cheape , and
mo e accu a e, and as polygenic and pha macogenomic
ools a e igo ously alida ed, genomic analyses will p o-
g essi ely mo e om special y clinics in o mains eam
ca diology. The u u e o ca dio ascula ca e is inc eas-
ingly p edic i e, p e en i e, and pe sonalised – ou chal-
lenge is o ansla e his genomic p omise in o equi able
bene i o e e y pa ien .
Lubomi Balabanski, PhD
Еdi o in cha ge o issue 2/2025
o Bulga ian Ca diology Jou nal
