Page 15 - The prevalence of the Val66Met polymorphism in musicians: Possible evidence for compensatory neuroplasticity from a pilot study

Konuma and Okada Inflammation and Regeneration (2021) 41:18 Page 4 of 5

genetic background by population stratification remains Conclusions
unclear. In another example, considerable differences of In this review, we focused on recent advances, utilities,
PRSs between the non-mainlanders and mainlanders in and perspectives of PRS. The predictive accuracy of PRS
Japan were reported [26]. In this report, PRS of BMI will continue to be improved by more extensive and
showed that the smaller BMI PRS was observed in non- diverse cohorts to construct PRS models and improve
mainlanders, although the greater BMI was observed in methods for PRS derivation and application. Although
non-mainlanders. This difference is assumed to be a re- further improvements of its comprehensiveness and
sult of sudden changes in environmental factors which generalizability would be needed for its clinical imple-
affected non-mainlanders’ BMI in the non-mainland that mentation in the future, the potential clinical impacts
preceded the reflection of genomic structure in response and benefits of the PRS have been proposed and dis-
to these environmental changes. From these examples, cussed. For example, PRS-informed clinical intervention,
the PRS could be susceptible to population structure’s PRS-informed disease screening, and PRS-informed life
geographical distributions, even within a relatively planning were proposed as the potential clinical benefits
homogeneous population. [5]. Also, individual PRS measurement only needs its
Third, given the numerous available models of PRS, it genome sequence, which could be taken once at a rela-
remains unclear which method is the most suitable for tively low cost, and PRS will be potentially applied for
predicting the risks of diseases or traits. It was reported various diseases and traits. PRS will guide therapeutic in-
that when categorizing the existing 15 PRS methods into terventions and lifestyle recommendations in several dis-
three groups, which consisted of (1) simple methods that eases. Thus, it might ultimately improve the health of an
selected variants below a p-value limit and within a LD entire population in the future.
range, (2) complex methods that selected variants by
attempting to approximate the results of a mixed-model Abbreviations
PRS: Polygenic risk score; SNP: Single nucleotide polymorphism;
approach, and (3) ensemble methods created by taking
GWAS: Genome-wide association study; AUC: Area under the curve;
an average of the top five PRSs weighted by their coeffi- ER: Estrogen receptor; BMI: Body mass index
cients in a cross-validated logistic regression, it was
shown that the simple methods generated slightly more Acknowledgements
Not applicable.
accurate PRSs than did the complex methods [27]. Fur-
ther insight into the characterization of PRS models will Authors’ contributions
be needed to evaluate and compare these predictive per- T.K. wrote the manuscripts. Y.O. supervised the review. The authors read and
formances. Comparable performance metrics of these approved the final manuscript.
PRS models would need to be systematically evaluated.
Funding
For example, the PGS Catalog [28], an open resource for This study was supported by the Japan Society for the Promotion of Science
PRSs that has been reported recently, enables PRS ana- (JSPS) KAKENHI (19H01021 and 20 K21834) and AMED (JP20km0405211,
lysis in a standardized format along with consistent JP20ek0109413, JP20ek0410075, JP20gm4010006, and 20 km0405217), Takeda
Science Foundation, and Bioinformatics Initiative of Osaka University
metadata and direct comparison between scores. Graduate School of Medicine, Osaka University. T.K. is an employee of Japan
Fourth, the prospect of clinical use of PRS is associated Tobacco Inc.
with a wide variety of ELSI (ethical, legal, and social im-
Availability of data and materials
plications) concerns, which have been also discussed in
Not applicable.
the context of monogenic genetic results and is also
present in the polygenic context [29]. One of the ELSI Declarations
concerns about PRS is the relevance of findings of PRS
Ethics approval and consent to participate
to family members. Genetic variation is shared in fam-
Not applicable.
ilies and the PRS of first-degree family members are cor-
related [30], but this information is not as clear as in the Consent for publication
monogenic genetic results. Guidelines developed by pro- Not applicable.
fessional societies would be needed for both patients and
Competing interests
providers for prompt warning about the polygenic risk
The authors declare that they have no competing interests.
to family members. Other examples of the ELSI con-
cerns about PRS are risk of psychosocial harms, false re- Author details
1 Department of Statistical Genetics, Osaka University Graduate School of
assurance, and overdiagnosis and overtreatment, which 2
Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan. Central Pharmaceutical
are typically considered in the monogenic genetic Research Institute, Japan Tobacco Inc., Takatsuki 569-1125, Japan. Laboratory
3
results. Further research for whether the harms of false of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC),
4
Osaka University, Suita 565-0871, Japan. Integrated Frontier Research for
reassurance, overtreatment and overdiagnosis materialize
Medical Science Division, Institute for Open and Transdisciplinary Research
would be needed. Initiatives, Osaka University, Suita 565-0871, Japan.