Back Pain without Disease or Substantial Injury in Children and Adolescents: A Twin Family Study Investigating Genetic Influence and Associations

This twin family study first aimed to investigate the evidence for genetic factors predicting the risk of lifetime prevalence of non-specific low back pain of at least three months duration (LBP (life)) and one-month current prevalence of thoracolumbar back pain (TLBP (current)) using a study of children, adolescents, and their first-degree relatives. Secondly, the study aimed to identify associations between pain in the back with pain in other regions and also with other conditions of interest. Randomly selected families (n = 2479) with child or adolescent twin pairs and their biological parents and first siblings were approached by Twins Research Australia. There were 651 complete twin pairs aged 6–20 years (response 26%). Casewise concordance, correlation, and odds ratios were compared for monozygous (MZ) and dizygous (DZ) pairs to enable inference about the potential existence of genetic vulnerability. Multivariable random effects logistic regression was used to estimate associations between LBP (life) or TLBP (current) as an outcome with the potentially relevant condition as predictors. The MZ pairs were more similar than the DZ pairs for each of the back pain conditions (all p values n = 1382). Data were consistent with the existence of genetic influences on the pain measures under the equal environments assumption of the classic twin model and associations with both categories of back pain were consistent with primary pain conditions and syndromes of childhood and adolescence which has research and clinical implications

Contrasting painless and painful phenotypes of pediatric restless legs syndrome : a twin family study

Objective: This study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders. Methods: In a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets. Results: Data were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04). Conclusions: Pediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS