From: The genetic basis of multiple sclerosis: a model for MS susceptibility
a_{h} | = | allelic frequency of the HLA DRB1*1501 susceptibility allele in the general population (only one copy needed for susceptibility) |
a_{hm} | = | allelic frequency of the HLA DRB1*1501 susceptibility allele in the MS population (a_{hm} = 0.328 in UCSF database) |
a_{1}, a_{2}, a_{3} | = | expected allelic frequency of dominant (a_{1}), recessive (a_{2}), and mixed (a_{3}) alleles at the non-HLA DRB1 loci in the general population |
a_{1m}, a_{2m}, a_{3m} | = | allelic frequency of dominant (a_{1m}), recessive (a_{2m}), and mixed (a_{3m}) alleles at the non-HLA DRB1 loci in an MS population |
F_{i}, F | = | unknown "frequency of susceptibility" (see text for definition) at the non-HLA loci in the general population (i = 1, 2,...x). [E(F_{i}) = F = h/r)] |
F_{m} | = | "frequency of susceptibility" at a non-HLA locus in an MS population |
h | = | known "frequency of susceptibility" at the HLA DRB1 locus in the general population (equal to the probability of having at least 1 copy of this allele) [h = 2a_{h} - (a_{h})^{2} = 0.24] |
h_{m} | = | known "frequency of susceptibility" at the HLA DRB1 locus in the MS population (equal to the probability of having at least 1 copy of this allele) [in the UCSF dataset; h_{m} = 0.55] |
P_{a1}, P_{a2}, P_{a3} | = | probability that a person in the general population has a "susceptible allelic state" (see text for definition) at dominant (P_{a1}), recessive (P_{a2}), and mixed (P_{a3}) non-HLA DRB1 loci. (P_{a1} = P_{a2} = P_{a3} = F = h/r) |
P_{h1} | = | probability that person with an HLA-negative sibling (not an identical- twin) has at least one copy of the HLA DRB1*1501 allele |
P_{H} | = | probability that an individual with an affected HLA DRB1*1501 positive sibling has at least one copy this gene |
P_{A1}, P_{A2}, P_{A3} | = | probability that an individual will inherit a "susceptible allelic state" given that their sibling is known to be in this state (see text for definition) at dominant (P_{a1}), recessive (P_{a2}), and mixed (P_{a3}) non-HLA DRB1 loci. |
x (x_{1}, x_{2}, x_{3}) | = | number of non-HLA DRB1susceptibility genetic loci involved in MS (dominant loci = x_{1}; recessive loci = x_{2}; mixed loci = x_{3}). [x_{1} + x_{2} + x_{3} = x] |
P_{HM} | = | Probability that an individual (from the general population) is both susceptible to getting MS and carries the HLA DRB1*1501 allele. (if Pt_{1} = Pt_{0}; then P_{HM} = h_{m}) |
P_{AM} | = | Probability that an individual (from the general population) who is both susceptible to getting MS and is in a susceptible state at a specific non-HLA DRB1 locus. (if Pt_{1} = Pt_{0}; then P_{AM} = F_{m}) |
r | = | ratio of the "frequency of susceptibility" at the HLA DRB1 locus to the average "frequency of susceptibility" at other non-HLA DRB1 loci. [r = h/F] |
n (n_{1}, n_{2}, n_{3}) | = | number of loci in "susceptible allelic states" required for MS to develop (dominant loci = n_{1}; recessive loci = n_{2}; mixed loci = n_{3}). [n_{1} + n_{2} + n_{3} = n] |
P[n] | = | probability of an individual in the general population possessing at least n loci in a "susceptible allelic state" |
C | = | proportion of patients, susceptible to MS, who do not have any copies of the HLA DRB1*1501 allele |
P[S] | = | probability that an individual in the general population is susceptible to MS This probability is the same as P(G). |
Pt | = | average penetrance of MS phenotype in susceptible patients. Also equal to the proband-wise monozygotic-twin concordance rate (CR_{MZ}). |
Pt* | = | average penetrance of MS phenotype in susceptible patients, adjusted for the shared intra-uterine and childhood environment of twins. [Pt* = (Pt) (2.9/5.4) = CR_{IG}] (See text) |
Pt_{1} | = | average penetrance of MS phenotype in susceptible patients with at least one copy of the HLA DRB1*1501 allele. Also equal to the proband-wise monozygotic-twin concordance rate (Z_{H+}) for this genotype. |
Pt_{0} | = | average penetrance of MS phenotype in susceptible patients without any copies of the HLA DRB1*1501 allele. Also equal to the proband-wise monozygotic-twin concordance rate (Z_{H-}) for this genotype |
P(MS_{H+}) | = | Probability of recurrence (i.e., the recurrence rate) in a family member of an MS proband who has at least one copy of the HLA DRB1*1501 allele. |
P(MS_{H-}) | = | Probability of recurrence (i.e., the recurrence rate) in a family member of an MS proband who lacks the HLA DRB1*1501 allele. |
P(MS) | = | prevalence of the MS phenotype in the general population (equated to the life-time probability of getting MS) |
P(MZ) | = | Probability of the 1^{st} twin of an MZ twin-pair getting MS: It is assumed that: P(MZ) = P(MS) |
P(MS | MZ) | = | Conditional probability of getting MS given that your MZ-twin has MS |
P(MS | DZ) | = | Conditional probability of getting MS given that your DZ-twin has MS |
P(MS | S) | = | Conditional probability of getting MS given that your sibling has MS |
P(G) | = | Probability of having any genotype capable of getting MS in response to some environmental exposure |
P(E) | = | Probability of receiving any environmental exposure (all factors) sufficient to cause MS in some susceptible individual |
CR_{MZ} | = | proband-wise monozygotic-twin concordance rate for MS. |
CR_{IG} | = | proband-wise monozygotic-twin concordance rate for MS adjusted for impact of a shared intrauterine environment. [CR_{IG} = (CR_{MZ}) (2.9/5.4)] This variable is the identical to (Pt*) but is used for clarity of the text. |
b' | = | CR_{IG}/P(G | IG) = P(MS, G, E | IG)/P(G | IG) |
CR_{DZ} | = | proband-wise dizygotic-twin concordance rate for MS. |
Z_{H+} | = | proband-wise monozygotic-twin concordance rate for MS when the proband possesses at least one copy of the HLA DRB1*1501 allele. |
Z_{H-} | = | proband-wise monozygotic-twin concordance rate for MS when the proband does not possess a copy of the HLA DRB1*1501 allele. |
CR_{S} | = | concordance rate for the MS phenotype in a non-twin sibling (1^{st} degree) |
CR_{PC} | = | concordance rate for the MS phenotype in a Parent or Child (1^{st} degree) |
CR_{AU} | = | concordance rate for the MS phenotype in an Aunt or Uncle (2^{nd} degree) |
CR_{FC} | = | concordance rate for the MS phenotype in a First Cousin (3^{rd} degree) |