Further Evidence Supporting a Parent‐of‐Origin Effect in Psoriatic Disease

Abstract

ObjectiveTo further explore the “parent‐of‐origin” effect in a large cohort of well‐phenotyped patients with cutaneous psoriasis without arthritis (PsC) and psoriatic arthritis (PsA).MethodsSelf‐reported family history was obtained from PsA patients from Toronto and Newfoundland satisfying the Classification of Psoriatic Arthritis criteria, and PsC patients from Toronto, who were examined by a rheumatologist to exclude PsA. Proportions of probands with paternally and maternally transmitted psoriatic disease were compared by McNemar's and chi‐square tests. Baseline clinical and genetic characteristics of probands with paternally and maternally transmitted disease were compared using logistic regression.ResultsA total of 849 probands reported a first‐degree relative affected with psoriatic disease (PsC or PsA), of which 532 (63%) reported an affected parent. A significantly larger proportion of probands reported an affected father compared to an affected mother with psoriatic disease (289 [57%] versus 220 [43%], respectively; P = 0.003). This paternal transmission bias was evident in PsA (P = 0.006) and PsC probands, although it did not reach statistical significance in PsC probands (P = 0.20). Furthermore, the proportion of paternal PsC–proband PsA pairs (161 of 214 paternal transmissions [75%]) was significantly larger than maternal PsC–proband PsA pairs (103 of 161 maternal transmissions [64%]) (P = 0.02). Newfoundland probands with paternally transmitted disease had higher HLA–B*08 carriage (P = 0.04) and lower MICA–129Met carriage (P = 0.03). Males had higher HLA–B*38 carriage (P = 0.05) and a higher prevalence of nail lesions (P = 0.01).ConclusionWe have provided further epidemiologic evidence of a paternal transmission bias in psoriatic disease.

Advances of Genomic Medicine in Psoriatic Arthritis

“…A significantly greater tendency of PsA probands to report an affected father compared to an affected mother has also been observed. In addition, these studies have also evidenced a significant reduction in the age of psoriasis onset in paternally transmitted cases, as well as an increase in the severity of PsA manifestations in subsequent generations [43][44][45]. These observations suggest that epigenetic modifications may contribute to the lack of heritability in Ps and PsA [46,47].…”

The effect of paternal psoriasis on neonatal outcomes: a nationwide population-based study

“…Moreover, no significant differences were noted in the clinical profiles of the disease between patients grouped by transmission pattern of psoriasis ( 36 ). However, in another large cohort study that recruited 849 patients ( 16 ), a greater chance of an increase in psoriasis severity was noted when psoriasis was transmitted by an affected father compared to an affected mother, and a significantly larger proportion of the probands were reported to have an affected father, suggesting a paternal transmission bias for psoriasis. In addition, further evidence has been provided through linkage analysis studies that have identified genetic loci possibly involved in paternal transmission of psoriasis ( 5 , 17 ).…”

Selection models for efficient two‐phase design of family studies

“…36 The general framework we have outlined here has been used primarily for the estimation of the effect of particular genetic markers of interest, but interest could lie in recruiting families with a view to better understanding parent of origin effects. 30,37 To do this, the design would be best recast using a Gaussian copula that admits a more general dependence structure within families. 6,8 In this case, interest may lie in estimating a function of the father-child and mother-child association parameters; see Zhong and Cook.…”