ABSTRACT
Deficits in phonological short-term memory and aspects of verb grammar morphology have been proposed as phenotypic markers of specific language impairment (SLI) with the suggestion that these traits are likely to be under different genetic influences. This investigation in 300 first-degree relatives of 93 probands with SLI examined familial aggregation and genetic linkage of two measures thought to index these two traits, non-word repetition and tense marking. In particular, the involvement of chromosomes 16q and 19q was examined as previous studies found these two regions to be related to SLI. Results showed a strong association between relatives' and probands' scores on non-word repetition. In contrast, no association was found for tense marking when examined as a continuous measure. However, significant familial aggregation was found when tense marking was treated as a binary measure with a cut-off point of -1.5 SD, suggestive of the possibility that qualitative distinctions in the trait may be familial while quantitative variability may be more a consequence of non-familial factors. Linkage analyses supported previous findings of the SLI Consortium of linkage to chromosome 16q for phonological short-term memory and to chromosome 19q for expressive language. In addition, we report new findings that relate to the past tense phenotype. For the continuous measure, linkage was found on both chromosomes, but evidence was stronger on chromosome 19. For the binary measure, linkage was observed on chromosome 19 but not on chromosome 16.
Subject(s)
Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 19/genetics , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Language Development Disorders/genetics , Memory Disorders/genetics , Child , Chromosome Mapping , DNA Mutational Analysis , Female , Genetic Testing , Genotype , Humans , Language , Language Tests , Learning Disabilities/genetics , Male , Memory, Short-Term/physiology , Phenotype , Verbal Behavior/physiologyABSTRACT
OBJECTIVE: The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors. DESIGN: We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale. RESULTS: Leptin and BMI showed substantial heritability (68.3% and 71.3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11beta-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5alpha-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63.8% (P = 0.012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5alpha-reductase activity. CONCLUSIONS: We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.
