使用多因素易患性阈值模型评估双相情感障碍的遗传度缺失

doi:10.3724/SP.J.1005.2014.0897

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HEREDITAS(Beijing) ›› 2014, Vol. 36 ›› Issue (9): 897-902.doi: 10.3724/SP.J.1005.2014.0897

• Research Articles • Previous Articles Next Articles

Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model

Kang Li^{1, 2}, Ruihuan Xu³, Hongde Zhang², Qian Wang¹

1. Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 2. Central Laboratory, Longgang District Central Hospital, Shenzhen 518116, China; 3. Clinical Laboratory, Longgang District Central Hospital, Shenzhen 518116, China

Received:2014-01-31 Online:2014-09-20 Published:2014-09-20

Abstract

Abstract: In order to evaluate the missing heritability of bipolar disorder, we queried the GWAS catalog of National Human Genome Research Institute, retrieve all the susceptible gene variation of bipolar disorder, and calculate the heritability explanation degree of each susceptibility variant using the multifactorial liability threshold model. The total heritability explanation degree of bipolar disorder was obtained through summing up the heritability explanation degree of each susceptibility variant. Then, we evaluated the missing heritability of bipolar disorder based on the total heritability explanation degree. The results showed that the total heritability explanation degree of bipolar disorder explained by known susceptible variants was 38.34%, and the other 61.66% of heritability can’t be explained by known susceptibility variants, which belong to the missing heritability of bipolar disorder. The total heritability explanation degree of bipolar disorder in this study was significantly increased compared to earlier similar studies abroad. With constant discovery of new bipolar disorder susceptibility variants, the missing heritability of bipolar disorder has been greatly reduced, but the missing heritability of bipolar disorder still exists and occupies a large part of the bipolar disorder heritability, indicating that the molecular genetic mechanisms of bipolar disorder need to be further clarified.

Key words: bipolar disorder, heritability, missing heritability, liability threshold model

Kang Li, Ruihuan Xu, Hongde Zhang, Qian Wang. Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model[J]. HEREDITAS(Beijing), 2014, 36(9): 897-902.

References

[1] J, Torgersen S, Røysanb E, Lygren S, Skre I, Onstad S, Øien PA. Heritability of bipolar spectrum disorders. Unity or heterogeneity? J Affect Disord , 2008, 106(3): 229-240.
[2] B. Personal genomes: The case of the missing heritability. Nature , 2008, 456(7218): 18-21.
[3] HC, Gui AHS, Cherny SS, Sham PC. Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases. Genet Epidemiol , 2011,35(5): 310-317.
[4] LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA , 2009, 106(23): 9362-9367.
[5] KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RMA, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry , 2007, 64(5): 543-552.
[6] HJ, Woo HG, Greenwood TA, Kripke DF, Kelsoe JR. A genome-wide association study of seasonal pattern mania identifies NF1A as a possible susceptibility gene for bipolar disorder. J Affect Disord , 2013, 145(2): 200-207.
[7] A, Mushiroda T, Kubo M, Takahashi A, Kamatani Y, Kamatani N, Stoianov D, Vazharova R, Karachanak S, Zaharieva I, Dimova I, Hadjidekova S, Milanova V, Madjirova N, Gerdjikov I, Tolev T, Poryazova N, O'Donovan MC, Owen MJ, Kirov G, Toncheva D, Nakamura Y. Genome-wide association study on bipolar disorder in the Bulgarian population. Genes Brain Behav , 2011, 10(7): 789-797.
[8] TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TFC, McCarroll SA, Visscher PM. Finding the missing heritability of complex diseases. Nature , 2009, 461(7265): 747-753.
[9] SH, Wray NR, Goddard ME, Visscher PM. Estimating missing heritability for disease from genome-wide asso-ciation studies. Am J Hum Genet , 2011, 88(3): 294-305.
[10] MF, Saad M, Bras J, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Büchel F, Sharma M, Gibbs JR, Schulte C, Moskvina V, Durr A, Holmans P, Kilarski LL, Guerreiro R, Hernandez DG, Brice A, Ylikotila P, Stef-ánsson H, Majamaa K, Morris HR, Williams N, Gasser T, Heutink P, Wood NW, Hardy J, Martinez M, Singleton AB, Nalls MA; International Parkinson's Disease Genomics Con-s-ortium (IPDGC); Wellcome Trust Case Control Consor-tium 2 (WTCCC2). Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson’s disease. Hum Mol Genet , 2012, 21(22): 4996-5009.
[11] 周钢桥)

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Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model

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