+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Multi-locus models of genetic risk of disease

, : Multi-locus models of genetic risk of disease. Genome Medicine 2(2): 10-10

Evidence for genetic contribution to complex diseases is described by recurrence risks to relatives of diseased individuals. Genome-wide association studies allow a description of the genetics of the same diseases in terms of risk loci, their effects and allele frequencies. To reconcile the two descriptions requires a model of how risks from individual loci combine to determine an individual's overall risk. We derive predictions of risk to relatives from risks at individual loci under a number of models and compare them with published data on disease risk. The model in which risks are multiplicative on the risk scale implies equality between the recurrence risk to monozygotic twins and the square of the recurrence risk to sibs, a relationship often not observed, especially for low prevalence diseases. We show that this theoretical equality is achieved by allowing impossible probabilities of disease. Other models, in which probabilities of disease are constrained to a maximum of one, generate results more consistent with empirical estimates for a range of diseases. The unconstrained multiplicative model, often used in theoretical studies because of its mathematical tractability, is not a realistic model. We find three models, the constrained multiplicative, Odds (or Logit) and Probit (or liability threshold) models, all fit the data on risk to relatives. Currently, in practice it would be difficult to differentiate between these models, but this may become possible if genetic variants that explain the majority of the genetic variance are identified.


PMID: 20181060

DOI: 10.1186/gm131

Other references

Huard, J.; Lochmüller, H.; Acsadi, G.; Jani, A.; Holland, P.; Guérin, C.; Massie, B.; Karpati, G., 1995: Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants. We demonstrated different transduction efficiency in several major organs of the immature (newborn) versus mature (adult) mice using adenoviral recombinants containing expression cassettes for either firefly luciferase or bacterial beta-galactosid...

Saravana, K.T.Pillai.; Son, J-Ho.; Hoefelmeyer, J.D., 2009: Bis(μ-dimesitylborinato-κO:O)bis-[(2-methyl-pyridine-κN)lithium. The title compound, [Li(2)(C(18)H(22)BO)(2)(C(6)H(7)N)(2)], is a lithium dimesitylboroxide dimer in which the lithium cation is also coordinated by one mol-ecule of 2-methyl-pyridine. At the core of the structure is an Li(2)O(2) four-membered ring...

Pevny, F.; Zabel, M.; Winter, R.F.; Rausch, A.F.; Yersin, H.; Tuczek, F.; Záliš, S., 2011: Improvement of (bipy)Pt(XR)2 (X=O, S) type photosensitizers by covalent dye attachment. Irradiation into the dye-based absorption band of complexes ((t)Bu(2)bipy)Pt(SR)(2) and ((t)Bu(2)bipy)Pt(OR)(2) where R denotes a coumarine-based thiolate and alkoxolate substituent populates the same excited triplet state as is obtained by excita...

Karakaya, G.; Kalyoncu, A.F., 2002: Experience of 11 years on analgesic intolerance in Turkey. NSAIDs are estimated to be responsible for up to 25% of all reported adverse drug reactions, ranging from urticaria and angioedema to asthmatic attacks and anaphylactic shock. This condition is problematic for both the patient who is frightened to...

Shridhar D.R.; Jogibhukta M.; Joshi P.P.; Rao C.S.; Junnarkar A.Y., 1984: Synthesis and biological activity of some new carboxamides carbohydrazides and carbamates derived from 2 3 dihydro 5h oxothiazolo 3 2 a pyrimidine 6 carboxylic acid. Indian Journal of Chemistry Section B Organic Chemistry Including Medicinal Chemistry 23(5): 492-494

Azam, F.M.rtimer, R.; Volcani, B., 1973: Germanium incorporation into the silica of diatom cell walls. Archiv fur Mikrobiologie: 92 (1) 11-20

Childress, J.J., 1995: Are there physiological and biochemical adaptations of metabolism in deep-sea animals?. From the earliest observations of deep-sea animals, it was obvious that they differed in many ways from shallower-living relatives. Over the years, there has been speculation that deep-sea animals have unusually low rates of biological activity; n...

Rengstorff, R.H., 1966: Observed effects of cycloplegia on refractive findings. Journal of the American Optometric Association 37(4): 360-360

Vannucchi, S.; Percario, Z.A.; Chiantore, M.V.; Matarrese, P.; Chelbi Alix, M.K.; Fagioli, M.; Pelicci, P.G.useppe; Malorni, W.; Fiorucci, G.; Romeo, G.; Affabris, E., 2000: Interferon-beta induces S phase showing via up-regulated expression of PML in squamous carcinoma cells. Type I Interferon (IFN) and all-trans retinoic acid (RA) inhibit cell proliferation of squamous carcinoma cell lines (SCC). Examinations of growth-affected cell populations show that SCC lines ME-180 and SiHa treated with IFN-beta undergo a specif...

Barry M.; Patterson J.E.; Tirrell S.; Cullen M.R.; Shope R.E., 1991: The effect of chloroquine prophylaxis on yellow fever vaccine antibody response comparison of plaque reduction neutralization test and elisa. Weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination. Experimental data indicate that chloroquine may inhibit yellow fever virus in vitro, yet there has been no clini...