Jumping on the train of personalized medicine: A primer for non-geneticist clinicians: Part 2. Fundamental concepts in genetic epidemiology

Current Psychiatry Reviews

Volumn 10, Issue 2, 2014, Pages 101-117

  Li, Aihua ^a   Meyre, David ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Genetic epidemiology; Genome wide association study; Guidelines; Heritability; Modes of inheritance; Nextgeneration sequencing; Study design

Indexed keywords

AUTOSOMAL DOMINANT INHERITANCE; AUTOSOMAL RECESSIVE INHERITANCE; CODOMINANCE; DNA EXTRACTION; GENE IDENTIFICATION; GENE SEQUENCE; GENE SILENCING; GENETIC ASSOCIATION; GENETIC DISORDER; GENETIC EPIDEMIOLOGY; GENETIC MARKER; GENOTYPE; HERITABILITY; HOMOZYGOSITY; HUMAN; LINKAGE ANALYSIS; MEDICAL PRACTICE; MOLECULAR GENETICS; PERSONALIZED MEDICINE; PHENOTYPE; PRACTICE GUIDELINE; PRIORITY JOURNAL; REVIEW; SEGREGATION ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84904737042     PISSN: 15734005     EISSN: 18756441     Source Type: Journal    
DOI: 10.2174/1573400510666140319235334     Document Type: Review

References (162)

1. Morton NE. The future of genetic epidemiology. Ann Med 1992; 24: 557-62.
2. Erk S, Meyer-Lindenberg A, Schmierer P, et al. Functional impact of a recently identified quantitative trait locus for hippocampal volume with genome-wide support. Transl Psychiatry 2013; 3: e287.
3. Li A, Meyre D. Challenges in reproducibility of genetic association studies: Lessons learned from the obesity field. Int J Obes (Lond) 2013; 37: 559-67.
4. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993; 72: 971-83.
5. Sudbery P, Sudbery I. Human molecular genetics. Third edition ed: Pearson Education Limited 2009.
6. Scriver CR. The PAH gene, phenylketonuria, and a paradigm shift. Hum Mutat 2007; 28: 831-45.
7. Ropers HH, Hamel BC. X-linked mental retardation. Nat Rev Genet 2005; 6: 46-57.
8. Strachan T, Read A. Human molecular genetics 4th ed: Garland Science 2011.
9. Raj A, Van Oudenaarden A. Nature, nurture, or chance: Stochastic gene expression and its consequences. Cell 2008; 135: 216-26.
10. Ben-Shachar S, Lanpher B, German JR, et al. Microdeletion 15q13. 3: A locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet 2009; 46: 382-8.
11. Van Bon BW, Mefford HC, Menten B, et al. Further delineation of the 15q13 microdeletion and duplication syndromes: A clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 2009; 46: 511-23.
12. Reik W, Walter J. Genomic imprinting: Parental influence on the genome. Nat Rev Genet 2001; 2: 21-32.
13. Miozzo M, Simoni G. The role of imprinted genes in fetal growth. Biol Neonate 2002; 81: 217-28.
14. Frost JM, Moore GE. The importance of imprinting in the human placenta. PLoS Genet 2010; 6: e1001015.
15. Nicholls RD. The impact of genomic imprinting for neurobehavioral and developmental disorders. J Clin Invest 2000; 105: 413-8.
16. Ruderfer DM, Chambert K, Moran J, et al. Mosaic copy number variation in schizophrenia. Eur J Hum Genet 2013.
17. McMahon FJ, Stine OC, Meyers DA, Simpson SG, DePaulo JR. Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet 1995; 56: 1277-86.
18. Goldstein JM, Faraone SV, Chen WJ, Tsuang MT. Gender and the familial risk for schizophrenia. Disentangling confounding factors. Schizophr Res 1992; 7: 135-40.
19. Rollins B, Martin MV, Sequeira PA, et al. Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. PLoS One 2009; 4: e4913.
20. Wermter AK, Scherag A, Meyre D, et al. Preferential reciprocal transfer of paternal/maternal DLK1 alleles to obese children: First evidence of polar overdominance in humans. Eur J Hum Genet 2008; 16: 1126-34.
21. Burghes AH, Vaessin HE, De La Chapelle A. Genetics. The land between Mendelian and multifactorial inheritance. Science 2001; 293: 2213-4.
22. Savage DB, Agostini M, Barroso I, et al. Digenic inheritance of severe insulin resistance in a human pedigree. Nat Genet 2002; 31: 379-84.
23. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 1990; 46: 222-8.
24. Burton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet 2005; 366: 941-51.
25. Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M. Genomewide scans of complex human diseases: True linkage is hard to find. Am J Hum Genet 2001; 69: 936-50.
26. Visscher PM, Hill WG, Wray NR. Heritability in the genomics era--concepts and misconceptions. Nat Rev Genet 2008; 9: 255-66.
27. Urbanoski KA, Kelly JF. Understanding genetic risk for substance use and addiction: A guide for non-geneticists. Clin Psychol Rev 2012; 32: 60-70.
28. Kamin LJ, Goldberger AS. Twin studies in behavioral research: A skeptical view. Theor Popul Biol 2002; 61: 83-95.
29. Falconer DS. The inheritance of liability to diseases with variable age of onset, with particular reference to diabetes mellitus. Ann Hum Genet 1967; 31: 1-20.
30. Ziegler A, Konig IR. A statistical approach to genetic epidemiology. 2nd ed: Wiley-VCH Verlag GmbH & Co. 2010.
31. Boomsma D, Busjahn A, Peltonen L. Classical twin studies and beyond. Nat Rev Genet 2002; 3: 872-82.
32. Carlsson S, Ahlbom A, Lichtenstein P, Andersson T. Shared genetic influence of BMI, physical activity and type 2 diabetes: A twin study. Diabetologia 2013; 56: 1031-5.
33. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: A tool for genome-wide complex trait analysis. Am J Hum Genet 2011; 88: 76-82.
34. Visscher PM, Yang J, Goddard ME. A commentary on 'common SNPs explain a large proportion of the heritability for human height'by Yang et al. (2010). Twin Res Hum Genet 2010; 13: 517-24.
35. Davies G, Tenesa A, Payton A, et al. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry 2011; 16: 996-1005.
36. Purcell SM, Wray NR, Stone JL, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748-52.
37. Dick DM, Riley B, Kendler KS. Nature and nurture in neuropsychiatric genetics: Where do we stand? Dialogues Clin Neurosci 2010; 12: 7-23.
38. Neel JV. Diabetes mellitus: A "thrifty" genotype rendered detrimental by "progress"? Am J Hum Genet 1962; 14: 353-62.
39. Elston RC. Segregation analysis. AdHum Genet 1981; 11: 63-120, 372-3.
40. Moll PP, Burns TL, Lauer RM. The genetic and environmental sources of body mass index variability: The Muscatine Ponderosity Family Study. Am J Hum Genet 1991; 49: 1243-55.
41. Barrai I, Cann HM. Segregation analysis of juvenile diabetes mellitus. J Med Genet 1965; 2: 8-11.
42. Martinez M. [Genetic markers and risk factors in diseases with complex etiology: psychiatric diseases]. Rev Epidemiol Sante Publique 1993; 41: 306-14.
43. Leitch CC, Zaghloul NA, Davis EE, et al. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet 2008; 40: 443-8.
44. Stoetzel C, Muller J, Laurier V, et al. Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am J Hum Genet 2007; 80: 1-11.
45. Risch NJ. Searching for genetic determinants in the new millennium. Nature 2000; 405: 847-56.
46. Farrall M. Quantitative genetic variation: A post-modern view. Hum Mol Genet 2004; 13: R1-7.
47. Eichler EE, Flint J, Gibson G, et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 2010; 11: 446-50.
48. Schork NJ, Greenwood TA, Braff DL. Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research. Schizophr Bull 2007; 33: 95-104.
49. Choquet H, Meyre D. Molecular basis of obesity: Current status and future prospects. Curr Genomics 2011; 12: 154-68.
50. Choquet H, Meyre D. Genetics of Obesity: What have we Learned? Curr Genomics 2011; 12: 169-79.
51. Lander ES. The new genomics: Global views of biology. Science 1996; 274: 536-9.
52. Reich DE, Lander ES. On the allelic spectrum of human disease. Trends Genet 2001; 17: 502-10.
53. Maher B. Personal genomes: The case of the missing heritability. Nature 2008; 456: 18-21.
54. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature 2009; 461: 747-53.
55. Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 2010; 11: 415-25.
56. Gudmundsson J, Sulem P, Gudbjartsson DF, et al. A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer. Nat Genet 2012; 44: 1326-9.
57. Rivas MA, Beaudoin M, Gardet A, et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 2011; 43: 1066-73.
58. Bonnefond A, Clement N, Fawcett K, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet 2012; 44: 297-301.
59. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB. Rare variants create synthetic genome-wide associations. PLoS Biol 2010; 8: e1000294.
60. Anderson CA, Soranzo N, Zeggini E, Barrett JC. Synthetic associations are unlikely to account for many common disease genome-wide association signals. PLoS Biol 2011; 9: e1000580.
61. Hunt KA, Mistry V, Bockett NA, et al. Negligible impact of rare autoimmune-locus coding-region variants on missing heritability. Nature 2013; 498: 232-5.
62. Goldstein DB, Chikhi L. Human migrations and population structure: What we know and why it matters. Annu Rev Genomics Hum Genet 2002; 3: 129-52.
63. Gibson G. Rare and common variants: Twenty arguments. Nat Rev Genet 2011; 13: 135-45.
64. ManolioTA, Bailey-Wilson JE, Collins FS. Genes, environment and the value of prospective cohort studies. Nat Rev Genet 2006; 7: 812-20.
65. Suarez E, Sariol CA, Burguete A, McLachlan G. A tutorial in genetic epidemiology and some considerations in statistical modeling. P R Health Sci J 2007; 26: 401-21.
66. Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K. A comprehensive review of genetic association studies. Genet Med 2002; 4: 45-61.
67. Meyre D, Delplanque J, Chevre JC, et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 2009; 41: 157-9.
68. Thomas D. Gene--environment-wide association studies: Emerging approaches. Nat Rev Genet 2010; 11: 259-72.
69. Moffitt TE, Caspi A, Rutter M. Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry 2005; 62: 473-81.
70. Yang J, Wray NR, Visscher PM. Comparing apples and oranges: Equating the power of casc-control and quantitative trait association studies. Genet Epidemiol 2010; 34: 254-7.
71. Cordell HJ, Barratt BJ, Clayton DG. Case/pseudocontrol analysis in genetic association studies: A unified framework for detection of genotype and haplotype associations, gene-gene and geneenvironment interactions, and parent-of-origin effects. Genet Epidemiol 2004; 26: 167-85.
72. Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancet 2003; 361: 598-604.
73. Cordell HJ, Clayton DG. Genetic association studies. Lancet 2005; 366: 1121-31.
74. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science 1996; 273: 1516-7.
75. Dawn Teare M, Barrett JH. Genetic linkage studies. Lancet 2005; 366: 1036-44.
76. Khoury MJ, Flanders WD. Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: Casecontrol studies with no controls. Am J Epidemiol 1996; 144: 207-13.
77. Piegorsch WW, Weinberg CR, Taylor JA. Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies. Stat Med 1994; 13: 153-62.
78. Kazma R, Dizier MH, Guilloud-Bataille M, Bonaiti-Pellie C, Genin E. Power comparison of different methods to detect genetic effects and gene-environment interactions. BMC Proc 2007; 1 Suppl 1: S74.
79. Yang Q, Khoury MJ, Sun F, Flanders WD. Case-only design to measure gene-gene interaction. Epidemiology 1999; 10: 167-70.
80. Pierce BL, Ahsan H. Case-only genome-wide interaction study of diseaserisk, prognosis and treatment. Genet Epidemiol 2010; 34: 7-15.
81. Visvikis S, Schlenck A, Maurice M. DNA extraction and stability for epidemiological studies. Clin Chem Lab Med 1998; 36: 551-5.
82. Kwok PY. Methods for genotyping single nucleotide polymorphisms. Annu Rev Genomics Hum Genet 2001; 2: 235-58.
83. Edenberg HJ, Liu Y. Laboratory methods for high-throughput genotyping. Cold Spring Harb Protoc 2009; 2009: pdb top62.
84. Song Y, You NC, Hsu YH, et al. FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring) 2008; 16: 2472-80.
85. Jurinke C, Van den Boom D, Cantor CR, Koster H. Automated genotyping using the DNA MassArray technology. Methods Mol Biol 2002; 187: 179-92.
86. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci U S A 1977; 74: 5463-7.
87. Hutchison CA 3rd. DNA sequencing: Bench to bedside and beyond. Nucleic Acids Res 2007; 35: 6227-37.
88. Metzker ML. Emerging technologies in DNA sequencing. Genome Res 2005; 15: 1767-76.
89. Venter JC. Genome-sequencing anniversary. The human genome at 10: Successes and challenges. Science 2011; 331: 546-7.
90. Mardis ER. The $1, 000 genome, the $100, 000 analysis? Genome Med 2010; 2: 84.
91. Ronaghi M, Karamohamed S, Pettersson B, Uhlen M, Nyren P. Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 1996; 242: 84-9.
92. Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet 2010; 11: 31-46.
93. Shendure J, Porreca GJ, Reppas NB, et al. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 2005; 309: 1728-32.
94. Rothberg JM, Hinz W, Rearick TM, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011; 475: 348-52.
95. Abecasis GR, Auton A, Brooks LD, et al. An integrated map of genetic variation from 1, 092 human genomes. Nature 2012; 491: 56-65.
96. Gonzaga-Jauregui C, Lupski JR, Gibbs RA. Human genome sequencing in health and disease. Annu Rev Med 2012; 63: 35-61.
97. Botstein D, Risch N. Discovering genotypes underlying human phenotypes: Past successes for mendelian disease, future approaches for complex disease. Nat Genet 2003; 33 Suppl: 228-37.
98. Kryukov GV, Pennacchio LA, Sunyaev SR. Most rare missense alleles are deleterious in humans: Implications for complex disease and association studies. Am J Hum Genet 2007; 80: 727-39.
99. Bamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 2011; 12: 745-55.
100. Kiezun A, Garimella K, Do R, et al. Exome sequencing and the genetic basis of complex traits. Nat Genet 2012; 44: 623-30.
101. O'Roak BJ, Vives L, Girirajan S, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012; 485: 246-50.
102. Sanders SJ, Murtha MT, Gupta AR, et al. De novomutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012; 485: 237-41.
103. Girard SL, Gauthier J, Noreau A, et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet 2011; 43: 860-3.
104. Krebs JE, Goldstein ES, Kilpatrick ST. Lewin's Gene X. 10th ed: Jones and Bartlet Publishers 2011.
105. Morton NE. Sequential tests for the detection of linkage. Am J Hum Genet 1955; 7: 277-318.
106. Polymeropoulos MH, Swift RG, Swift M. Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. Nat Genet 1994; 8: 95-7.
107. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet 1998; 20: 143-8.
108. Blackwelder WC, Elston RC. A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol 1985; 2: 85-97.
109. Davies JL, Kawaguchi Y, Bennett ST, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994; 371: 130-6.
110. Arya R, Duggirala R, Almasy L, et al. Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans. Nat Genet 2002; 30: 102-5.
111. Saunders CL, Chiodini BD, Sham P, et al. Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring) 2007; 15: 2263-75.
112. Lander ES, Botstein D. Homozygosity mapping: A way to map human recessive traits with the DNA of inbred children. Science 1987; 236: 1567-70.
113. Chiang AP, Beck JS, Yen HJ, et al. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a BardetBiedl syndrome gene (BBS11). Proc Natl Acad Sci U S A 2006; 103: 6287-92.
114. Zhu M, Zhao S. Candidate gene identification approach: Progress and challenges. Int J Biol Sci 2007; 3: 420-7.
115. Tranchevent LC, Capdevila FB, Nitsch D, De Moor B, De Causmaecker P, Moreau Y. A guide to web tools to prioritize candidate genes. Brief Bioinform 2011; 12: 22-32.
116. Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467-72.
117. Pericak-Vance MA, Bebout JL, Gaskell PC Jr., et al. Linkage studies in familial Alzheimer disease: Evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48: 1034-50.
118. Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet 2012; 90: 7-24.
119. Craddock N, Sklar P. Genetics of bipolar disorder. Lancet 2013; 381: 1654-62.
120. Ripke S, Sanders AR, Kendler KS, et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969-76.
121. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 2009; 14: 10-7.
122. Pearson TA, Manolio TA. How to interpret a genome-wide association study. JAMA 2008; 299: 1335-44.
123. Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010; 363: 166-76.
124. Gilissen C, Hoischen A, Brunner HG, Veltman JA. Disease gene identification strategies for exome sequencing. Eur J Hum Genet 2012; 20: 490-7.
125. Abecasis GR, Altshuler D, Auton A, et al. A map of human genome variation from population-scale sequencing. Nature 2010; 467: 1061-73.
126. Becker J, Semler O, Gilissen C, etal. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 2011; 88: 362-71.
127. Ioannidis JP. Why most published research findings are false. PLoS Med 2005; 2: e124.
128. Zollner S, Pritchard JK. Overcoming the winner's curse: Estimating penetrance parameters from case-control data. Am J Hum Genet 2007; 80: 605-15.
129. Zhong H, Prentice RL. Correcting "winner's curse" in odds ratios from genomewide association findings for major complex human diseases. Genet Epidemiol 2010; 34: 78-91.
130. Fawcett KA, Wheeler E, Morris AP, et al. Detailed investigation of the role of common and low-frequency WFS1 variants in type 2 diabetes risk. Diabetes 2010; 59: 741-6.
131. Do R, Kathiresan S, Abecasis GR. Exome sequencing and complex disease: Practical aspects of rare variant association studies. Hum Mol Genet 2012; 21: R1-9.
132. Pompanon F, Bonin A, Bellemain E, Taberlet P. Genotyping errors: Causes, consequences and solutions. Nat Rev Genet 2005; 6: 847-59.
133. Anderson CA, Pettersson FH, Clarke GM, Cardon LR, Morris AP, Zondervan KT. Data quality control in genetic case-control association studies. Nat Protoc 2010; 5: 1564-73.
134. Wittke-Thompson JK, Pluzhnikov A, Cox NJ. Rational inferences about departures from Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 967-86.
135. Chan EY. Next-generation sequencing methods: Impact of sequencing accuracy on SNP discovery. Methods Mol Biol 2009; 578: 95-111.
136. Stitziel NO, Kiezun A, Sunyaev S. Computational and statistical approaches to analyzing variants identified by exome sequencing. Genome Biol 2011; 12: 227.
137. Ku CS, Cooper DN, Polychronakos C, Naidoo N, Wu M, Soong R. Exome sequencing: Dual role as a discovery and diagnostic tool. Ann Neurol 2012; 71: 5-14.
138. Garner C. Confounded by sequencing depth in association studies of rare alleles. Genet Epidemiol 2011; 35(4): 2618.
139. Slager SL, Schaid DJ. Case-control studies of genetic markers: Power and sample size approximations for Armitage's test for trend. Hum Hered 2001; 52: 149-53.
140. Saito YA, Talley NJ, De Andrade M, Petersen GM. Case-control genetic association studies in gastrointestinal disease: Review and recommendations. Am J Gastroenterol 2006; 101: 1379-89.
141. Burton PR, Scurrah KJ, Tobin MD, Palmer LJ. Covariance components models for longitudinal family data. Int J Epidemiol 2005; 34: 1063-77; discussion 77-9.
142. Li B, Leal SM. Methods for detecting associations with rare variants for common diseases: Application to analysis of sequence data. Am J Hum Genet 2008; 83: 311-21.
143. Wu MC, Lee S, Cai T, Li Y, Boehnke M, Lin X. Rare-variant association testing for sequencing data with the sequence kernel association test. Am J Hum Genet 2011; 89: 82-93.
144. Rice TK, Schork NJ, Rao DC. Methods for handling multiple testing. Adv Genet 2008; 60: 293-308.
145. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol 2008; 32: 227-34.
146. Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet 2003; 361: 865-72.
147. Bretz F, Landgrebe J, Brunner E. Multiplicity issues in microarray experiments. Methods Inf Med 2005; 44: 431-7.
148. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 2003; 100: 9440-5.
149. Goldstein DB, Allen A, Keebler J, et al. Sequencing studies in human genetics: design and interpretation. Nat Rev Genet 2013; 14: 460-70.
150. Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet 2006; 7: 781-91.
151. Tao S, Feng J, Webster T, et al. Genome-wide two-locus epistasis scans in prostate cancer using two European populations. Hum Genet 2012; 131: 1225-34.
152. Greliche N, Germain M, Lambert JC, et al. A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis. BMC Med Genet 2013; 14: 36.
153. Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet 2005; 6: 287-98.
154. Franks PW. Gene x environment interactions in type 2 diabetes. Curr Diab Rep 2011; 11: 552-61.
155. Pare G, Cook NR, Ridker PM, Chasman DI. On the use of variance per genotype as a tool to identify quantitative trait interaction effects: A report from the Women's Genome Health Study. PLoS Genet 2010; 6: e1000981.
156. Purcell S, Neale B, Todd-Brown K, et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559-75.
157. Normand SL. Meta-analysis: Formulating, evaluating, combining, and reporting. Stat Med 1999; 18: 321-59.
158. Minelli C, Thompson JR, Abrams KR, Thakkinstian A, Attia J. The quality of meta-analyses of genetic association studies: A review with recommendations. Am J Epidemiol 2009; 170: 1333-43.
159. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-60.
160. Neupane B, Loeb M, Anand SS, Beyene J. Meta-analysis of genetic association studies under heterogeneity. Eur J Hum Genet 2012; 20: 1174-81.
161. Peerbooms OL, Van Os J, Drukker M, et al. Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: Evidence for a common genetic vulnerability? Brain Behav Immun 2011; 25: 1530-43.
162. Ripke S, Wray NR, Lewis CM, et al. A mega-analysis of genomewide association studies for major depressive disorder. Mol Psychiatry 2013; 18: 497-511.