Explicating heterogeneity of complex traits has strong potential for improving GWAS efficiency

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Kulminski, Alexander M ^a   Loika, Yury ^a   Culminskaya, Irina ^a   Arbeev, Konstantin G ^a   Ukraintseva, Svetlana V ^a   Stallard, Eric ^a   Yashin, Anatoliy I ^a  

^a DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIPID;

BODY MASS; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; PHENOTYPE; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM; STATISTICS AND NUMERICAL DATA;

BODY MASS INDEX; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; LIPIDS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; SAMPLE SIZE;

EID: 84991688445     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep35390     Document Type: Article

References (39)

1. Sierra, F., Hadley, E., Suzman, R. & Hodes, R. Prospects for life span extension. Annu Rev Med 60, 457-469, doi: 10.1146/annurev. med.60.061607.220533 (2009).
2. Olshansky, S. J., Perry, D., Miller, R. A. & Butler, R. N. Pursuing the longevity dividend: scientific goals for an aging world. Ann N Y Acad Sci 1114, 11-13, doi: 10.1196/annals.1396.050 (2007).
3. Aging, N. I. o. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging http://www.nia.nih.gov/sites/default/ files/strategic-plan108.pdf (2010) (Date of access: May, 15).
4. Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic acids research 42, D1001-D1006, doi: 10.1093/nar/gkt1229 (2014).
5. Gibson, G. Rare and common variants: twenty arguments. Nat Rev Genet 13, 135-145, doi: 10.1038/nrg3118 (2011).
6. Eichler, E. E. et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 11, 446-450, doi: 10.1038/nrg2809 (2010).
7. MacRae, C. A. & Vasan, R. S. Next-generation genome-wide association studies: time to focus on phenotype? Circ Cardiovasc Genet 4, 334-336, doi: 10.1161/CIRCGENETICS.111.960765 (2011).
8. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747-753, doi: 10.1038/nature08494 (2009).
9. Yashin, A. I. et al. Genetics of aging, health, and survival: dynamic regulation of human longevity related traits. Front Genet 6, 122, doi: 10.3389/fgene.2015.00122 (2015).
10. Day-Williams, A. G. & Zeggini, E. The effect of next-generation sequencing technology on complex trait research. Eur J Clin Invest 41, 561-567, doi: 10.1111/j.1365-2362.2010.02437.x (2011).
11. Kidambi, S. et al. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans. BMC Med Genet 13, 27, doi: 10.1186/1471-2350-13-27 (2012).
12. Kulminski, A. M. et al. Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the apolipoprotein e4 allele on lifespan. PLoS Genet 10, e1004141, doi: 10.1371/journal.pgen.1004141 (2014).
13. Yashin, A. I. et al. How the quality of GWAS of human lifespan and health span can be improved. Front Genet 4, 125, doi: 10.3389/ fgene.2013.00125 (2013).
14. Yashin, A. I. et al. How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity. Biogerontology doi: 10.1007/s10522-015-9594-8 (2015).
15. Martin, G. M. Epigenetic gambling & epigenetic drift as potential mechanisms underlying the quasi-stochastic distributions of late life neurodegenerative disorders. Molecular Neurodegeneration 7, L20, doi: 10.1186/1750-1326-7-s1-l20 (2012).
16. Willer, C. J. et al. Discovery and refinement of loci associated with lipid levels. Nat Genet 45, 1274-1283, doi: 10.1038/ng.2797 (2013).
17. Kulminski, A. M. Unraveling genetic origin of aging-related traits: evolving concepts. Rejuvenation Res 16, 304-312, doi: 10.1089/ rej.2013.1441 (2013).
18. Nesse, R. M. & Williams, G. C. Why we get sick: the new science of Darwinian medicine 1st edn (Times Books, 1994).
19. Teslovich, T. M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707-713, doi: 10.1038/ nature09270 (2010).
20. Speliotes, E. K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42, 937-948, doi: 10.1038/ng.686 (2010).
21. Locke, A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197-206, doi: 10.1038/ nature14177 (2015).
22. Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S. & Hirschhorn, J. N. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33, 177-182, doi: 10.1038/ng1071 (2003).
23. Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci 14, 365-376, doi: 10.1038/nrn3475 (2013).
24. Dobzhansky, T. Nothing in biology makes sense except in the light of evolution. The American Biology Teacher 35, 125-129, doi: 10.2307/4444260 (1973).
25. Vijg, J. & Suh, Y. Genetics of longevity and aging. Annu Rev Med 56, 193-212, doi: 10.1146/annurev.med.56.082103.104617 (2005).
26. Oeppen, J. & Vaupel, J. W. Demography. Broken limits to life expectancy. Science 296, 1029-1031, doi: 10.1126/science.1069675 (2002).
27. De Benedictis, G. & Franceschi, C. The unusual genetics of human longevity. Science of aging knowledge environment: SAGE KE 2006, pe20, doi: 10.1126/sageke.2006.10.pe20 (2006).
28. Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38, 904-909, doi: 10.1038/ng1847 (2006).
29. Yashin, A. I. et al. Genetic Structures of Population Cohorts Change with Increasing Age: Implications for Genetic Analyses of Human aging and Life Span. Ann Gerontol Geriatr Res 1 (2014).
30. Schork, N. J. Personalized medicine: Time for one-person trials. Nature 520, 609-611, doi: 10.1038/520609a (2015).
31. Graff, M. et al. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course. Hum Mol Genet 22, 3597-3607, doi: 10.1093/hmg/ddt205 (2013).
32. Nygaard, M. et al. Birth cohort differences in the prevalence of longevity-associated variants in APOE and FOXO3A in Danish longlived individuals. Exp Gerontol 57, 41-46, doi: 10.1016/j.exger.2014.04.018 (2014).
33. Kulminski, A. M. et al. The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging Cell 12, 237-246, doi: 10.1111/acel.12046 (2013).
34. Jarvik, G. P. et al. Genetic influences on age-related change in total cholesterol, low density lipoprotein-cholesterol, and triglyceride levels: longitudinal apolipoprotein E genotype effects. Genet Epidemiol 11, 375-384, doi: 10.1002/gepi.1370110407 (1994).
35. Atzmon, G. et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 4, e113 (2006).
36. Yashin, A. I. et al. Genes, demography, and life span: the contribution of demographic data in genetic studies on aging and longevity. Am J Hum Genet 65, 1178-1193 (1999).
37. Rao, C. R. Linear statistical inference and its applications (John Wiley & Sons, Inc., 1965).
38. Chiani, M., Dardari, D. & Simon, M. K. New exponential bounds and approximations for the computation of error probability in fading channels. Ieee T Wirel Commun 2, 840-845, doi: 10.1109/Twc.2003.814350 (2003).
39. Kendall, M. G. & Stuart, A. The advanced theory of statistics: 3 vol. (Charles Griffin, 1968).