Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease

Trends in Neurosciences

Volumn 37, Issue 12, 2014, Pages 733-741

  Flint, Jonathan ^a   Timpson, Nicholas ^b   Munafò, Marcus ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOPHENOTYPE; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HUMAN; MENTAL DISEASE; PHENOTYPE; REVIEW; CHROMOSOME MAP; GENETIC PREDISPOSITION; GENETICS; PROCEDURES; SINGLE NUCLEOTIDE POLYMORPHISM;

CHROMOSOME MAPPING; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MENTAL DISORDERS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84919666255     PISSN: 01662236     EISSN: 1878108X     Source Type: Journal    
DOI: 10.1016/j.tins.2014.08.007     Document Type: Review

References (97)

1. Ripke S., et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat. Genet. 2013, 45:1150-1159.
2. Sklar P., et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat. Genet. 2011, 43:977-983.
3. Ripke S., et al. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 2011, 43:969-976.
4. Walsh T., et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008, 320:539-543.
5. Xu B., et al. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat. Genet. 2008, 40:880-885.
6. Sebat J., et al. Strong association of de novo copy number mutations with autism. Science 2007, 316:445-449.
7. Malhotra D., et al. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 2011, 72:951-963.
8. Vissers L.E., et al. A de novo paradigm for mental retardation. Nat. Genet. 2010, 42:1109-1112.
9. Xu B., et al. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat. Genet. 2011, 43:864-868.
10. Girard S.L., et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat. Genet. 2011, 43:860-863.
11. O'Roak B.J., et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Genet. 2011, 43:585-589.
12. Walters J.T., Owen M.J. Endophenotypes in psychiatric genetics. Mol. Psychiatry 2007, 12:886-890.
13. Kendler K.S., Neale M.C. Endophenotype: a conceptual analysis. Mol. Psychiatry 2010, 15:789-797.
14. Surguladze S.A., et al. Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Neuropsychology 2004, 18:212-218.
15. Brewer W.J., et al. Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. Am. J. Psychiatry 2005, 162:71-78.
16. Fuller R., et al. Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am. J. Psychiatry 2002, 159:1183-1189.
17. Toulopoulou T., et al. Impaired intellect and memory: a missing link between genetic risk and schizophrenia?. Arch. Gen. Psychiatry 2010, 67:905-913.
18. Owens S.F., et al. Genetic overlap between episodic memory deficits and schizophrenia: results from the Maudsley Twin Study. Psychol. Med. 2011, 41:521-532.
19. Toulopoulou T., et al. Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples. Arch. Gen. Psychiatry 2007, 64:1348-1355.
20. Broer L., et al. Distinguishing true from false positives in genomic studies: p values. Eur. J. Epidemiol. 2013, 28:131-138.
21. Flint J., Munafo M.R. The endophenotype concept in psychiatric genetics. Psychol. Med. 2007, 37:163-180.
22. Hindorff L.A., et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:9362-9367.
23. Button K.S., et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 2013, 14:365-376.
24. Hulshoff Pol H.E., et al. Overlapping and segregating structural brain abnormalities in twins with schizophrenia or bipolar disorder. Arch. Gen. Psychiatry 2012, 69:349-359.
25. Harms M.P., et al. Structural abnormalities in gyri of the prefrontal cortex in individuals with schizophrenia and their unaffected siblings. Br. J. Psychiatry 2010, 196:150-157.
26. Brans R.G., et al. Heritability of changes in brain volume over time in twin pairs discordant for schizophrenia. Arch. Gen. Psychiatry 2008, 65:1259-1268.
27. Stein J.L., et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nat. Genet. 2012, 44:552-561.
28. Taal H.R., et al. Common variants at 12q15 and 12q24 are associated with infant head circumference. Nat. Genet. 2012, 44:532-538.
29. Ikram M.A., et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nat. Genet. 2012, 44:539-544.
30. Bis J.C., et al. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nat. Genet. 2012, 44:545-551.
31. Need A.C., et al. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum. Mol. Genet. 2009, 18:4650-4661.
32. Calkins M.E., et al. The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite coll-aboration. Schizophr. Bull. 2007, 33:33-48.
33. Greenwood T.A., et al. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch. Gen. Psychiatry 2007, 64:1242-1250.
34. Greenwood T.A., et al. Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am. J. Psychiatry 2013, 170:521-532.
35. Mowry B.J., et al. The molecular genetics of schizophrenia: an update. Aust. N. Z. J. Psychiatry 1997, 31:704-713.
36. Lewis C.M., et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am. J. Hum. Genet. 2003, 73:34-48.
37. Teslovich T.M., et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010, 466:707-713.
38. Dehghan A., et al. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 2011, 123:731-738.
39. Kottgen A., et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat. Genet. 2013, 45:145-154.
40. van der Harst P., et al. Seventy-five genetic loci influencing the human red blood cell. Nature 2012, 492:369-375.
41. Lango Allen H., et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 2010, 467:832-838.
42. Speliotes E.K., et al. Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 2010, 42:937-948.
43. Wray N.R., et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol. Psychiatry 2012, 17:36-48.
44. Park J.H., et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 2010, 42:570-575.
45. Yang J., et al. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 2010, 42:565-569.
46. Purcell S., et al. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003, 19:149-150.
47. Duman R.S., et al. A molecular and cellular theory of depression. Arch. Gen. Psychiatry 1997, 54:597-606.
48. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000, 23:477-501.
49. Samuels B.A., Hen R. Neurogenesis and affective disorders. Eur. J. Neurosci. 2011, 33:1152-1159.
50. Turner C.A., et al. The fibroblast growth factor family: neuromodulation of affective behavior. Neuron 2012, 76:160-174.
51. Luscher B., et al. The GABAergic deficit hypothesis of major depressive disorder. Mol. Psychiatry 2011, 16:383-406.
52. McGowan P.O., et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 2009, 12:342-348.
53. Paul I.A., Skolnick P. Glutamate and depression: clinical and preclinical studies. Ann. N. Y. Acad. Sci. 2003, 1003:250-272.
54. Mann J.J. Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 1999, 21:99S-105S.
55. Sanacora G., et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch. Gen. Psychiatry 2004, 61:705-713.
56. Lees C.W., et al. New IBD genetics: common pathways with other diseases. Gut 2011, 60:1739-1753.
57. Beecham A.H., et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 2013, 45:1353-1360.
58. McCarthy M.I. Genomics, type 2 diabetes, and obesity. N. Engl. J. Med. 2010, 363:2339-2350.
59. Kendler K.S. What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. Mol. Psychiatry 2013, 18:1058-1066.
60. Sborgi L., et al. Characterization of a novel interaction between Bcl-2 members Diva and Harakiri. PLoS ONE 2010, 5:e15575.
61. Litterman N., et al. An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning. PLoS Biol. 2011, 9:e1001060.
62. Coyle-Thompson C.A., Banerjee U. The strawberry notch gene functions with Notch in common developmental pathways. Development 1993, 119:377-395.
63. Wang K., et al. Analysing biological pathways in genome-wide association studies. Nat. Rev. Genet. 2010, 11:843-854.
64. Walters J.T., et al. The role of the major histocompatibility complex region in cognition and brain structure: a schizophrenia GWAS follow-up. Am. J. Psychiatry 2013, 170:877-885.
65. Ferreira M.A., et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat. Genet. 2008, 40:1056-1058.
66. Purcell S.M., et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009, 460:748-752.
67. Browner W.S., Newman T.B. Are all significant P values created equal? The analogy between diagnostic tests and clinical research. JAMA 1987, 257:2459-2463.
68. Zimmerman M., et al. Diagnostic co-morbidity in 2300 psychiatric out-patients presenting for treatment evaluated with a semi-structured diagnostic interview. Psychol. Med. 2008, 38:199-210.
69. Angst J. Comorbidity of anxiety, phobia, compulsion and depression. Int. Clin. Psychopharmacol. 1993, 8(Suppl 1):21-25.
70. Blazer D.G., et al. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am. J. Psychiatry 1994, 151:979-986.
71. Kessler R.C., et al. Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. Br. J. Psychiatry 1996, 168:17-30.
72. Merikangas K.R., et al. Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force. Br. J. Psychiatry 1996, (Suppl 30):58-67.
73. Pini S., et al. Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia. J. Affect. Disord. 1997, 42:145-153.
74. Mineka S., et al. Comorbidity of anxiety and unipolar mood disorders. Annu. Rev. Psychol. 1998, 49:377-412.
75. Kessler R.C., et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003, 289:3095-3105.
76. Alonso J., et al. 12-Month comorbidity patterns and associated factors in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr. Scand. 2004, (Suppl 420):28-37.
77. Hunt C., et al. Generalized anxiety disorder and major depressive disorder comorbidity in the National Survey of Mental Health and Well-Being. Depress. Anxiety 2004, 20:23-31.
78. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013, 381:1371-1379. Consortium, C-D.G.o.t.P.G.
79. Cross-Disorder Group of the Psychiatric Genomics Consortium Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 2013, 45:984-994.
80. Krug A., et al. Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage 2010, 49:1831-1836.
81. Krug A., et al. A genome-wide supported variant in CACNA1C influences hippocampal activation during episodic memory encoding and retrieval. Eur. Arch. Psychiatry Clin. Neurosci. 2014, 264:103-110.
82. Thimm M., et al. Effects of a CACNA1C genotype on attention networks in healthy individuals. Psychol. Med. 2011, 41:1551-1561.
83. Wessa M., et al. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol. Psychiatry 2010, 15:1126-1127.
84. Jogia J., et al. The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Mol. Psychiatry 2011, 16:1070-1071.
85. Bigos K.L., et al. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch. Gen. Psychiatry 2010, 67:939-945.
86. Erk S., et al. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch. Gen. Psychiatry 2010, 67:803-811.
87. Cannon T.D., Keller M.C. Endophenotypes in the genetic analyses of mental disorders. Annu. Rev. Clin. Psychol. 2006, 2:267-290.
88. Vrieze S.I., et al. Confluence of genes, environment, development, and behavior in a post Genome-Wide Association Study world. Dev. Psychopathol. 2012, 24:1195-1214.
89. Gottesman I.I., Gould T.D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 2003, 160:636-645.
90. Spencer C.C., et al. Designing genome-wide association studies: sample size, power, imputation, and the choice of genotyping chip. PLoS Genet. 2009, 5:e1000477.
91. Thorgeirsson T.E., et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 2008, 452:638-642.
92. Ware J.J., et al. Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis. Nicotine Tob. Res. 2011, 13:1167-1175.
93. Fowler C.D., et al. Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature 2011, 471:597-601.
94. Munafo M.R., et al. Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. J. Natl. Cancer Inst. 2012, 104:740-748.
95. Smith G.D., Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int. J. Epidemiol. 2004, 33:30-42.
96. Wamsley E.J., et al. Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation?. Biol. Psychiatry 2012, 71:154-161.
97. Chen Y., et al. Variations in DNA elucidate molecular networks that cause disease. Nature 2008, 452:429-435.