유럽인 자료로 산출된 양극성 장애 다유전자 위험 점수의 한국인 양극성 장애 환자에의 적용
Polygenic Risk Scores for Bipolar Disorder in Korean Populations in Comparison to European Populations
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Objectives This study examined whether the polygenic risk score (PRS) calculated from the most recent genome-wide association study for bipolar disorder (BD) of European ancestry patients is significantly associated with BD diagnosis in the Korean population. Methods The study included 417 Korean patients with BD and 497 healthy controls. Genotyping was performed using the Korean Biobank Array. Summary statistics of the European samples from the Psychiatric Genomic Consortium were used as base data to generate the PRS for each individual. The program PRSice-2 was used to calculate the PRS. Logistic regression was conducted to determine the association between BD diagnosis and PRS for BD after adjusting for age and sex. Results PRS for BD was significantly higher in patients diagnosed with BD compared to healthy controls. The PRS at the p-value threshold of 0.01 best explained the variance of BD after adjusting for age and sex (R2=0.0061, p=0.039). Subgroup analyses were performed for bipolar I and II subgroups. In bipolar I patients, the PRS at the p-value threshold of 0.01 best explained the diagnosis (R2=0.0165, p=0.0055), whereas no significant result was found for bipolar II patients. Conclusion PRS for BD calculated for the Korean sample showed a significant association with the BD diagnosis. This result suggests an overlapping genetic risk for BD between the European and Korean populations.
Abstract
Objectives This study examined whether the polygenic risk score (PRS) calculated from the most recent genome-wide association study for bipolar disorder (BD) of European ancestry patients is significantly associated with BD diagnosis in the Korean population. Methods The study included 417 Korean patients with BD and 497 healthy controls. Genotyping was performed using the Korean Biobank Array. Summary statistics of the European samples from the Psychiatric Genomic Consortium were used as base data to generate the PRS for each individual. The program PRSice-2 was used to calculate the PRS. Logistic regression was conducted to determine the association between BD diagnosis and PRS for BD after adjusting for age and sex. Results PRS for BD was significantly higher in patients diagnosed with BD compared to healthy controls. The PRS at the p-value threshold of 0.01 best explained the variance of BD after adjusting for age and sex (R2=0.0061, p=0.039). Subgroup analyses were performed for bipolar I and II subgroups. In bipolar I patients, the PRS at the p-value threshold of 0.01 best explained the diagnosis (R2=0.0165, p=0.0055), whereas no significant result was found for bipolar II patients. Conclusion PRS for BD calculated for the Korean sample showed a significant association with the BD diagnosis. This result suggests an overlapping genetic risk for BD between the European and Korean populations.
참고문헌 (30)
- Grande I, "Bipolar disorder", Lancet, 387, pp.1561~1572 (2016)
- Bauer M, "Epidemiology of bipolar disorders", Epilepsia, 46(Suppl 4), pp.8~13 (2005)
- Weissman MM, "Cross-national epidemiology of major depression and bipolar disorder", JAMA, 276, pp.293~299 (1996)
- Tsuchiya KJ, "Risk factors in relation to an emergence of bipolar disorder : a systematic review", Bipolar Disord, 5, pp.231~242 (2003)
- Craddock N, "Genetics of bipolar disorder", J Med Genet, 36, pp.585~594 (1999)
- McGuffin P, "The heritability of bipolar affective disorder and the genetic relationship to unipolar depression", Arch Gen Psychiatry, 60, pp.497~502 (2003)
- Jamain S, "Common and rare variant analysis in early-onset bipolar disorder vulnerability", PLoS One, 9, pp.e104326~ (2014)
- Bush WS, "Chapter 11 : genome-wide association studies", PLoS Comput Biol, 8, pp.e1002822~ (2012)
- Ferreira MA, "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder", Nat Genet, 40, pp.1056~1058 (2008)
- Psychiatric GWAS Consortium Bipolar Disorder Working Group, "Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4", Nat Genet, 43, pp.977~983 (2011)
- Yang J, "GCTA : a tool for genome-wide complex trait analysis", Am J Hum Genet, 88, pp.76~82 (2011)
- Bulik-Sullivan BK, "LD score regression distinguishes confounding from polygenicity in genome-wide association studies", Nat Genet, 47, pp.291~295 (2015)
- Dudbridge F, "Power and predictive accuracy of polygenic risk scores", PLoS Genet, 9, pp.e1003348~ (2013)
- Choi SW, "Tutorial: a guide to performing polygenic risk score analyses", Nat Protoc, 15, pp.2759~2772 (2020)
- Visscher PM, "10 years of GWAS discovery: biology, function, and translation", Am J Hum Genet, 101, pp.5~22 (2017)
- Purcell SM, "Common polygenic variation contributes to risk of schizophrenia and bipolar disorder", Nature, 460, pp.748~752 (2009)
- Barnett JH, "The genetics of bipolar disorder", Neuroscience, 164, pp.331~343 (2009)
- Johansson V, "A population-based heritability estimate of bipolar disorder-In a Swedish twin sample", Psychiatry Res, 278, pp.180~187 (2019)
- Aminoff SR, "Polygenic risk scores in bipolar disorder subgroups", J Affect Disord, 183, pp.310~314 (2015)
- Coombes BJ, "Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores", Transl Psychiatry, 10, pp.314~ (2020)
- Chen DT, "Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder", Mol Psychiatry, 18, pp.195~205 (2013)
- Talarico F, "Implications of an admixed Brazilian population in schizophrenia polygenic risk score", Schizophr Res, 204, pp.404~406 (2019)
- 이진영, "유럽인 자료로 산출된 조현병 다유전자 위험도 점수의 한국인 조현병 환자를 대상으로 한 적용", 대한조현병학회지, 23(2), pp.65~70 (2020), 대한조현병학회[DOI]
- Choi SW, "PRSice-2: polygenic risk score software for biobank-scale data", Gigascience, 8 (2019)
- Stahl EA, "Genome-wide association study identifies 30 loci associated with bipolar disorder", Nat Genet, 51, pp.793~803 (2019)
- Li HJ, "Novel risk loci associated with genetic risk for bipolar disorder among Han Chinese individuals : a genome-wide association study and meta-analysis", JAMA Psychiatry, 78, pp.320~330 (2021)
- Baek JH, "Psychopathologic structure of bipolar disorders: exploring dimensional phenotypes, their relationships, and their associations with bipolar I and II disorders", Psychol Med, 49, pp.2177~2185 (2019)
- Baek JH, "Differences between bipolar I and bipolar II disorders in clinical features, comorbidity, and family history", J Affect Disord, 131, pp.59~67 (2011)
- Baek JH, "Association between the zinc finger protein 804A(ZNF804A)gene and the risk of schizophrenia and bipolar I disorder across diagnostic boundaries", Bipolar Disord, 19, pp.305~313 (2017)
- Mistry S, "The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression : a systematic review", J Affect Disord, 234, pp.148~155 (2018)
