Does genetic anticipation occur in familial rheumatoid arthritis?

Abstract

Objective-To determine if there is evidence for genetic anticipation in rheumatoid arthritis (RA) by analysing the possibility that parental disease status and age at proband conception influence the age of onset and disease severity of the proband. Method-RA outpatients were identified and data were also taken from Newcastle multicase RA pedigrees. Comparisons of age of onset and parental age at proband conception were made for pedigrees grouped according to the disease status of the parents. Correlation coefficients and linear regression models were calculated for the age of RA onset in the probands. Measures of disease severity were compared in RA mother-proband pairs.Results-The results were similar in both the outpatient (n = 153) and multicase pedigree (n = 15) samples. Significant results were confined to pedigrees in which the mother had RA (20 of the outpatient probands and seven of the multicase group). Probands in these sibships had a younger age of RA onset than their affected mothers (38-3 years (95% confidence interval (CI) 33-8 to 42.8) versus 53 7 (47.3 to 60 0) (p = 0.002) in the outpatient sample; 32-4 years (25.3 to 39.6) versus 43*4 years (29.0 to 57.9) (p = 0.1) in the multicase pedigrees). In the maternal RA group, both the maternal and paternal age at proband conception showed significant negative correlations (r = -0 65, p = 0-002 and r = -0-60, p = 0-005, respectively in the outpatient sample) and linear regression coefficients with age of proband disease onset. In seven affected mother-proband pairs, the probands had a tendency to more severe disease, despite shorter disease duration and younger age.

A new statistical test for age-of-onset anticipation: Application to bipolar disorder

“…Reports of AOA now exist for, among other diseases, myotonic dystrophy [Höweler et al, 1989], schizophrenia [Bassett and Honer, 1994], rheumatoid arthritis [Deighton et al, 1994], and hereditary dentatorubral-pallidoluysian atrophy [Sano et al, 1994]. Most recently, Paterson et al [1996] found strong statistical evidence of AOA for breast cancer, colon cancer, Alzheimer's disease, and maturity-onset diabetes mellitus.…”

Estimation of Kendall’s tau for bivariate doubly truncated data

“…The cause of AOA has been identified as DNA instability, such as nucleotide repeats that change in length in subsequent generations, which alters the phenotype of the disease. Reports of AOA exist in literatures, such as bipolar disorder (McInnis, McMahon, Stine, & Ross, 1993), facioscapulohumeral muscular dystrophy (Zatz et al, 1995), schizophrenia (Bassett & Honer, 1994), rheumatoid arthritis (Deighton, Heslop, McDonagh, Walker, & Thomson, 1994). Recently, changes in disease phenotype in subsequent generations also have been identified in other disorders, such as in colon cancer, breast cancer, Alzheimer disease and diabetes (Nilbert, Timshel, Bernstein, & Larsen, 2009;Paterson, Kennedy, & Petronis, 1996).…”

Assessing changes in ages at onset over successive generation: An application to breast cancer

“…Decreased age at onset (DAO) in successive generations has been reported for a number of diseases, including Huntington's disease [Ranen et al, 1995], Crohn's disease [Polito et al, 1996], familial primary pulmonary hypertension [Loyd et al, 1995], and familial rheumatoid arthritis [Deighton et al, 1994]. DAO has also been reported for some cancers, including breast cancer [Lindblom, 1995;Paterson et al, 1996], colon cancer [Paterson et al, 1996], testicular germ-cell tumors [Dieckmann et al, 1993], and leukemia [Horwitz et al, 1996].…”