Genetic and environmental components of thyroxine variation in Mennonites from Kansas and Nebraska

L.J. MARTIN1 AND M.H. CRAWFORD1

Abstract Thyroxine is an endocrine hormone that regulates cellular and organismic metabolism. Current research on thyroxine has primarily examined its adaptive potential and genetic inheritance patterns. To date, no studies have attempted to investigate the interaction between the genetic and environmental components of thyroxine variation. This approach is useful because hormones are on feedback regulation; thus interaction occurs between the environment and gene expression. The purposes of this research are to characterize the genetic and environmental components of thyroxine variation using univariate statistics and to estimate the genetic and cultural heritabilities through path analysis. For univariate analyses, analyses of variance are used to determine whether or not age, sex, or community affiliation are covariates of thyroxine level. Significant differences existed in thyroxine level based on sex and community affiliation (p

KEY WORDS: HORMONES, THYROXINE, ENDOCRINE SYSTEM, PHYSIOLOGY, MENNONITES

Thyroxine is a hormone in the endocrine system that regulates cellular and organismic metabolism and governs calorigenesis, lipid, carbohydrate, and protein metabolism, respiratory and cardiovascular function, and growth and development (Butt 1975; Hardy 1981). There are two forms of this hormone: thyroxine (T^sub 4^) and triiodothyronine (T^sub 3^). T^sub 3^ is recognized as the metabolically active form of thyroxine (Butt 1975; Hardy 1981). Compared to T^sub 3^, T^sub 4^ is secreted at a ratio of 20 to 1 and is less responsive to environmental influences (Harland and Orr 1975; Hardy 1981; Danforth 1986). Current research on thyroxine focuses primarily on its metabolic functions, although a few studies have examined its adaptive potential (Schwartz 1983; Riis and Madsen 1985; Ballard 1986; Legrand 1986; Pimentel 1987; Cabello and Wrutniak 1990; Maruo et al. 1992a,b; Sower et al. 1992; Facchini et al. 1997). For example, thyroid hormone fluctuations have been reported in cold adaptation studies and a relationship between thyroxine and physique has been suggested (Reed et al. 1986,1990, 1992; Silverin et al. 1989; Gaikwad et al. 1990; Kwiecinski et al. 1991; Rone et al. 1992; Kirchengast 1994).

To date, no studies have attempted to explain thyroxine variation by focusing on the interaction between genetic, environmental, and endocrinological factors. However, integrating information from several disciplines is particularly informative when studying hormones such as thyroxine because of their complex interrelationships. It is important to identify both the genetic and the environmental components of normal thyroxine variation because thyroxine variation is due to both genetic and environmental factors. The goals of this research are to examine the genetic and environmental components involved in thyroxine variation using univariate statistics and to estimate the genetic and cultural heritabilities using path analysis.

Materials and Methods

Population. The data for this study were collected from three Mennonite communities, two in Kansas (Goessel and Meridian) and one in Nebraska (Henderson) (Figure 1), as part of a multidisciplinary study of biological aging. The collected data included demographics, reproductive histories, blood specimens, nutritional data, anthropometrics, genealogies, psychological questionnaires, and neuromuscular tests (Crawford and Rogers 1982). Crawford and Rogers (1982) demonstrated that Goessel and Henderson are most similar genetically because they both originated from a single community, Alexanderwohl, during the 1870s. In contrast, Meridian is genetically heterogeneous because it was recently founded by a charismatic leader and consisted of several familial groupings of various origins. Data Collection and Analysis. From November 1980 to January 1981 data were collected from 1062 Mennonites, ranging in age from 18 to 94 years, from the 3 communities (Goessel, Henderson, and Meridian). Individuals who had a history of thyroid disease were excluded from the analysis, thus reducing the sample used in this study to 1042 individuals (Goessel, 460 individuals; Meridian, 85 individuals; Henderson, 497 individuals). The total sample of 1042 individuals was included in the computation of univariate statistics. However, only family data were used for the path analysis, thus reducing the sample to 378 individuals representing 112 families (Ill fathers, 112 mothers, and 155 children).

To assess thyroxine levels, we drew blood specimens from nonfasting volunteers. The serum T4 levels were assayed using the standard radioimmunoassay technique of Consolidated Biomedical Laboratories (Roche Labs, Wichita, Kansas) immediately after the blood was drawn.

Univariate Methods. Univariate methods were used to examine population and individual differences. For population level analyses means, standard deviations, and standard errors of thyroxine levels for the three Mennonite communities were compared to each other and to the normal physiological variation. For individual level analyses age effects were examined by regressing thyroxine variation on age and on age-squared. Sex differences in thyroxine level were analyzed using a one-way analysis of variance (ANOVA). Furthermore, thyroxine levels for females were partitioned into pre- and postmenopausal groups and were compared using ANOVA. Last, the postmenopausal women were separated into those who had complete hysterectomies (surgical menopause) versus those who had experienced menopause without hysterectomies (natural menopause), and the thyroxine levels were compared using ANOVA.