Table 1 Model Definitions and Abriviations
From: The genetic basis of multiple sclerosis: a model for MS susceptibility
ah | = | allelic frequency of the HLA DRB1*1501 susceptibility allele in the general population (only one copy needed for susceptibility) |
ahm | = | allelic frequency of the HLA DRB1*1501 susceptibility allele in the MS population (ahm = 0.328 in UCSF database) |
a1, a2, a3 | = | expected allelic frequency of dominant (a1), recessive (a2), and mixed (a3) alleles at the non-HLA DRB1 loci in the general population |
a1m, a2m, a3m | = | allelic frequency of dominant (a1m), recessive (a2m), and mixed (a3m) alleles at the non-HLA DRB1 loci in an MS population |
Fi, F | = | unknown "frequency of susceptibility" (see text for definition) at the non-HLA loci in the general population (i = 1, 2,...x). [E(Fi) = F = h/r)] |
Fm | = | "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 = 2ah - (ah)2 = 0.24] |
hm | = | 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; hm = 0.55] |
Pa1, Pa2, Pa3 | = | probability that a person in the general population has a "susceptible allelic state" (see text for definition) at dominant (Pa1), recessive (Pa2), and mixed (Pa3) non-HLA DRB1 loci. (Pa1 = Pa2 = Pa3 = F = h/r) |
Ph1 | = | probability that person with an HLA-negative sibling (not an identical- twin) has at least one copy of the HLA DRB1*1501 allele |
PH | = | probability that an individual with an affected HLA DRB1*1501 positive sibling has at least one copy this gene |
PA1, PA2, PA3 | = | 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 (Pa1), recessive (Pa2), and mixed (Pa3) non-HLA DRB1 loci. |
x (x1, x2, x3) | = | number of non-HLA DRB1susceptibility genetic loci involved in MS (dominant loci = x1; recessive loci = x2; mixed loci = x3). [x1 + x2 + x3 = x] |
PHM | = | Probability that an individual (from the general population) is both susceptible to getting MS and carries the HLA DRB1*1501 allele. (if Pt1 = Pt0; then PHM = hm) |
PAM | = | 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 Pt1 = Pt0; then PAM = Fm) |
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 (n1, n2, n3) | = | number of loci in "susceptible allelic states" required for MS to develop (dominant loci = n1; recessive loci = n2; mixed loci = n3). [n1 + n2 + n3 = 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 (CRMZ). |
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) = CRIG] (See text) |
Pt1 | = | 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 (ZH+) for this genotype. |
Pt0 | = | 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 (ZH-) for this genotype |
P(MSH+) | = | 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(MSH-) | = | 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 1st 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 |
CRMZ | = | proband-wise monozygotic-twin concordance rate for MS. |
CRIG | = | proband-wise monozygotic-twin concordance rate for MS adjusted for impact of a shared intrauterine environment. [CRIG = (CRMZ) (2.9/5.4)] This variable is the identical to (Pt*) but is used for clarity of the text. |
b' | = | CRIG/P(G | IG) = P(MS, G, E | IG)/P(G | IG) |
CRDZ | = | proband-wise dizygotic-twin concordance rate for MS. |
ZH+ | = | proband-wise monozygotic-twin concordance rate for MS when the proband possesses at least one copy of the HLA DRB1*1501 allele. |
ZH- | = | proband-wise monozygotic-twin concordance rate for MS when the proband does not possess a copy of the HLA DRB1*1501 allele. |
CRS | = | concordance rate for the MS phenotype in a non-twin sibling (1st degree) |
CRPC | = | concordance rate for the MS phenotype in a Parent or Child (1st degree) |
CRAU | = | concordance rate for the MS phenotype in an Aunt or Uncle (2nd degree) |
CRFC | = | concordance rate for the MS phenotype in a First Cousin (3rd degree) |