Race/Ethnic Differences in Birth Size, Infant Growth, and Body Mass Index at Age Five Years in Children in Hawaii.

BACKGROUND: Factors at birth and infancy may increase risk of being overweight in childhood. The aim of this study was to examine the relationship of birth size and infant growth (2-24 months) with BMI at age 5 years in a multiethnic population. METHODS: This was a retrospective study (using electronic medical records of a health maintenance organization in Hawaii) of singleton children born in 2004-2005, with linked maternal and birth information, infant weights (n = 597) and lengths (n = 473) in the first 2 years, and BMI measures at age 5 years (n = 894). Multiple regression models were used to estimate the association of BMI at age 5 years with birth size and infant growth. RESULTS: Birth weight was positively associated with BMI at age 5 years, adjusting for gestational age, sex, race/ethnicity, and maternal prepregnancy weight, age, education, and smoking. A greater change in infant weight was associated with a higher BMI at age 5 years, though the effect of birth weight on BMI was neither mediated nor modified by infant growth rate. Birth weight, change in infant weight, and BMI at age 5 years varied by race/ethnicity. Change in infant BMI in the first 2 years was higher in other Pacific Islanders and whites (Δ = 0.966; confidence interval [CI] = 0.249-1.684; p = 0.02) than in Asian, other, and part Native Hawaiian race/ethnic groups. CONCLUSIONS: Early biological measures of birth weight and infant weight gain varied by race/ethnicity and positively predicted BMI at age 5 years.

Genetic variation in the raptor gene is associated with overweight but not hypertension in American men of Japanese ancestry.

BACKGROUND: The mechanistic target of rapamycin (mTOR) pathway is pivotal for cell growth. Regulatory associated protein of mTOR complex I (Raptor) is a unique component of this pro-growth complex. The present study tested whether variation across the raptor gene (RPTOR) is associated with overweight and hypertension. METHODS: We tested 61 common (allele frequency ≥ 0.1) tagging single nucleotide polymorphisms (SNPs) that captured most of the genetic variation across RPTOR in 374 subjects of normal lifespan and 439 subjects with a lifespan exceeding 95 years for association with overweight/obesity, essential hypertension, and isolated systolic hypertension. Subjects were drawn from the Honolulu Heart Program, a homogeneous population of American men of Japanese ancestry, well characterized for phenotypes relevant to conditions of aging. Hypertension status was ascertained when subjects were 45-68 years old. Statistical evaluation involved contingency table analysis, logistic regression, and the powerful method of recursive partitioning. RESULTS: After analysis of RPTOR genotypes by each statistical approach, we found no significant association between genetic variation in RPTOR and either essential hypertension or isolated systolic hypertension. Models generated by recursive partitioning analysis showed that RPTOR SNPs significantly enhanced the ability of the model to accurately assign individuals to either the overweight/obese or the non-overweight/obese groups (P = 0.008 by 1-tailed Z test). CONCLUSION: Common genetic variation in RPTOR is associated with overweight/obesity but does not discernibly contribute to either essential hypertension or isolated systolic hypertension in the population studied.

Genetic analysis of TOR complex gene variation with human longevity: a nested case-control study of American men of Japanese ancestry.

The mechanistic target of rapamycin (mTOR) pathway is crucial for life span determination in model organisms. The aim of the present study was to test tagging single-nucleotide polymorphisms that captured most of the genetic variation across key TOR complex 1 (TORC1) and TOR complex 2 (TORC2) genes MTOR, RPTOR, and RICTOR and the important downstream effector gene RPS6KA1 for association with human longevity (defined as attainment of at least 95 years of age) as well as health span phenotypes. Subjects comprised a homogeneous population of American men of Japanese ancestry, well characterized for aging phenotypes and who have been followed for 48 years. The study used a nested case-control design involving 440 subjects aged 95 years and older and 374 controls. It found no association of 6 tagging single-nucleotide polymorphisms for MTOR, 61 for RPTOR, 7 for RICTOR, or 5 for RPS6KA1 with longevity. Of 40 aging-related phenotypes, no significant association with genotype was seen. Thus common genetic variation (minor allele frequency ≥10%) in MTOR, RPTOR, RICTOR, and RPS6KA1 is not associated with extreme old age or aging phenotypes in this population. Further research is needed to assess the potential genetic contribution of other mTOR pathway genes to human longevity, gene expression, upstream and downstream targets, and clinically relevant aging phenotypes.

Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry.

OBJECTIVES: To determine the relation between height, FOXO3 genotype and age of death in humans. METHODS: Observational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. A Cox regression model with age as the time scale, stratified by year of birth, was used to estimate the effect of baseline height on mortality during follow-up. An analysis of height and longevity-associated variants of the key regulatory gene in the insulin/IGF-1 signaling (IIS) pathway, FOXO3, was performed in a HHP-HAAS subpopulation. A study of fasting insulin level and height was conducted in another HHP-HAAS subpopulation. RESULTS: A positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003-1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002-1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10-0.42; P = 0.001). CONCLUSION: Height in mid-life is positively associated with mortality, with shorter stature predicting longer lifespan. Height was, moreover, associated with fasting insulin level and the longevity genotype of FOXO3, consistent with a mechanistic role for the IIS pathway.

Association analyses of insulin signaling pathway gene polymorphisms with healthy aging and longevity in Americans of Japanese ancestry.

Evidence from model organisms suggests that the insulin/IGF-1 signaling pathway has an important, evolutionarily conserved influence over rate of aging and thus longevity. In humans, the FOXO3 gene is the only widely replicated insulin/IGF-1 signaling pathway gene associated with longevity across multiple populations. Therefore, we conducted a nested case-control study of other insulin/IGF-1 signaling genes and longevity, utilizing a large, homogeneous, long-lived population of American men of Japanese ancestry, well characterized for aging phenotypes. Genotyping was performed of single nucleotide polymorphisms, tagging most of the genetic variation across several genes in the insulin/IGF-1 signaling pathway or related gene networks that may be influenced by FOXO3, namely, ATF4, CBL, CDKN2, EXO1, and JUN. Two initial, marginal associations with longevity did not remain significant after correction for multiple comparisons, nor were they correlated with aging-related phenotypes.

FOXO3 gene variants and human aging: coding variants may not be key players.

FOXO3 is generally recognized as a "master" gene in aging since its association with longevity has been replicated in multiple organisms and human populations. A group of single nucleotide polymorphisms in linkage disequilibrium with a coding region has been associated with human longevity, but the actual functional variant is unidentified. Therefore, we sequenced the coding region in our long-lived Japanese American population in order to enhance resources for fine mapping this region. We demonstrate that of 38 published variants, 6 are misalignments with homologous nonallelic sequences from FOXO3B (ZNF286B), a pseudogene on a different chromosome; 2 are attributable to ZNF286B only, and the remaining 30 were unconfirmed, indicating that they are very rare and not likely involved in longevity. Furthermore, we identified a novel, unique, nonsynonymous coding variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic groups but appeared too rare for major longevity effects in our study populations.

Characteristics of women who sought emergency contraception at a university-based women's health clinic.

OBJECTIVE: The purpose of this study was to identify unique characteristics for seeking emergency contraception (EC) among sexually active unmarried women who attended a university-based women's health clinic (WHC). STUDY DESIGN: Three hundred nine consecutive women who attended the women's health clinic for 3 months of the 2006 spring semester completed an anonymous self-administered questionnaire. Fisher exact and Student t tests were used to assess bivariate associations, and step-wise regression was used to determine independent associations. RESULTS: Women who requested EC were more likely to have previously used EC (P < .001), to have had unprotected sex in the past 6 months (P < .001), to have experienced an unintended pregnancy in the past year (P = .009), and to perceive the need for EC use in the next 3 months (P < .001) but were less likely to use hormonal contraception or an intrauterine device (P < .001). CONCLUSION: Our findings support the need for increased education that would include the use of and access to effective primary contraceptive methods in conjunction with EC awareness.

A prospective study of high-density lipoprotein cholesterol, cholesteryl ester transfer protein gene variants, and healthy aging in very old Japanese-american men.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP). METHODS: Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD442G and Int 14A). RESULTS: HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p =.002) but not related to non-CVD (p =.147) or total (p =.547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Int 14A variant. These men also had higher HDL-C levels (p =.047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p =.005). CONCLUSIONS: Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging.

FOXO3A genotype is strongly associated with human longevity.

Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations.

Absence of evidence for an association between resistin gene variants and insulin resistance in an Asian population with low and high blood pressure.

AIMS: Although the function of resistin in human biology is unclear, some evidence suggests resistin gene variants influence insulin resistance, and insulin resistance-related hypertension. We searched for associations between common resistin gene variants and factors related to insulin resistance in Asian individuals with high or low blood pressure (BP). METHODS: Non-diabetic Chinese or Japanese sibling pairs were included if one had extreme hypertension and the other was either hypertensive or hypotensive. Four common, non-coding single nucleotide polymorphisms (SNPs) were identified by sequencing the resistin gene in 24 hypertensive probands. Generalized estimating equations (GEEs)-based regressions were then performed to test for SNP associations using the entire study population (n=1556). RESULTS: Of 72 tests, only one was significant at the 0.05 level; 3.5 significant tests were expected by chance alone. High variability in insulin and triglyceride levels created wide confidence intervals, thus the negative results are not conclusive for these phenotypes. However, the large sample size resulted in narrow confidence intervals for BMI, fasting and 120min post-load glucose, and high and low density lipoprotein cholesterol (LDL-C). CONCLUSION: Several factors associated with insulin resistance are not likely influenced by the resistin gene in non-diabetic Asian individuals with high and low blood pressure.

Midlife risk factors and healthy survival in men.

CONTEXT: Healthy survival has no clear phenotypic definition, and little is known about its attributes, particularly in men. OBJECTIVE: To test whether midlife biological, lifestyle, and sociodemographic risk factors are associated with overall survival and exceptional survival (free of a set of major diseases and impairments). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study within the Honolulu Heart Program/Honolulu Asia Aging Study. A total of 5820 Japanese American middle-aged men (mean age, 54 [range, 45-68] years) free of morbidity and functional impairments were followed for up to 40 years (1965-2005) to assess overall and exceptional survival. Exceptional survival was defined as survival to a specified age (75, 80, 85, or 90 years) without incidence of 6 major chronic diseases and without physical and cognitive impairment. MAIN OUTCOME MEASURE: Overall survival and exceptional survival. RESULTS: Of 5820 original participants, 2451 participants (42%) survived to age 85 years and 655 participants (11%) met the criteria for exceptional survival to age 85 years. High grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia were associated with exceptional survival, and lack of a marital partner was associated with mortality before age 85 years. Risk factor models based on cumulative risk factors (survival risk score) suggest that the probability of survival to oldest age is as high as 69% with no risk factors and as low as 22% with 6 or more risk factors. The probability of exceptional survival to age 85 years was 55% with no risk factors but decreased to 9% with 6 or more risk factors. CONCLUSION: These data suggest that avoidance of certain risk factors in midlife is associated with the probability of a long and healthy life among men.

Asian adolescents have a higher trunk:peripheral fat ratio than Whites.

Body fat, especially in the upper body, has been associated with increased risk of chronic disease among adults. Factors associated with these traits among ethnically diverse populations are not well studied. We examined factors influencing body fat and weight among Asian and White adolescent girls from the female adolescent maturation longitudinal study (initial exam plus 2-y follow-up examination) in Hawaii. The objective of this study was to identify and compare influences on and differences in body size and fat distribution among Asian and White adolescent girls. Subjects were identified among age-eligible members of a large HMO. Of the 214 girls recruited for Exam 1, 107 girls returned for Exam 2. The girls' age, ethnicity, a 3-d diet record, and physical activity recall were obtained by questionnaire at both times, and Tanner pubic hair stage and anthropometry were clinically measured by trained staff at both exams. The ethnic proportion of the study sample was 57% Asian and 43% White. Each girl's ethnicity was based on the ethnic proportion of each biologic parent. The percentage of body fat was measured by Lunar Prodigy dual energy X-ray absorptiometry (DXA) at the follow-up exam only. Among various measures of skeletal size and adiposity, only leg length (inversely) and DXA trunk:peripheral fat ratio (directly) were associated with proportion of Asian ethnicity, after adjusting for age, Tanner pubic hair stage, physical activity, and energy intake. In a multivariate analysis focusing on the trunk:peripheral fat ratio, this measure of central obesity was positively associated with proportion of Asian ethnicity (P = 0.001) and bi-iliac breadth (P = 0.002), and negatively associated with birth weight (P = 0.021), after adjustment for Tanner pubic hair stage, physical activity, energy intake, biacromial breadth, and height. In conclusion, Asian adolescents have a higher trunk:peripheral fat ratio than Whites. Adolescent bi-iliac breadth (positively) and birthweight (negatively) are associated with more body fat on the trunk vs. periphery during adolescence.

Ethnicity and nutrition of adolescent girls in Hawaii.

OBJECTIVE: To describe the ethnicity and nutrition of adolescent girls in Hawaii. DESIGN: This was a cross-sectional survey. SUBJECTS: Girls, aged 9 to 14 years, were identified from the membership files of Kaiser Permanente Hawaii, a large Hawaii health maintenance organization. MAIN OUTCOME MEASURES: Nutrient and food group intakes were compared against recommended intakes, physical activity levels, and anthropometric measurements of height, weight, body mass index (BMI), and subscapular and iliac skinfold thicknesses. STATISTICAL ANALYSIS PERFORMED: Asian girls, girls of mixed ethnicity, and white girls were compared using analysis of variance. RESULTS: Although Asian girls weighed the least and were the most sedentary, white girls had the lowest BMIs. Mixed ethnicity girls had the highest weights, BMIs, and subscapular and iliac skinfold thicknesses. No significant differences were found in major macronutrient intake. However, mixed ethnicity and Asian girls had lower fiber, iron, folate, and calcium intake than white girls. All groups met recommendations for iron intake, whereas none met fiber and calcium recommendations. All girls met folate recommendations. No differences were found in intakes for tofu, soy, grains, vegetables, or fruit and nuts food groups. Mixed ethnicity girls had the highest sweetened carbonated beverage intake although overall sugar intake was highest in white girls. Asian and mixed ethnicity girls' meat intakes were higher than white girls'. Intakes of mixed ethnicity girls more closely resembled those of Asians, although they exhibited the highest BMIs. CONCLUSIONS: These data suggest grain, vegetable, fruit, and dairy intake should be encouraged as part of a balanced diet for adolescent girls in Hawaii.

Volcano related atmospheric toxicants in Hilo and Hawaii Volcanoes National Park: implications for human health.

Volcanic fog (vog) from Kilauea volcano on the island of Hawaii includes a variety of chemical species including sulfur compounds and traces of metals such as mercury. The metal species seen tended to be in the nanograms per cubic meter range, whereas oxides of sulfur: SO2 and SO3 and sulfate aerosols, were in the range of micrograms per cubic meter and rarely even as high as a few milligrams per cubic meter of air (nominally ppb to ppm). These sulfur species are being investigated for associations with both acute and chronic changes in human health status. The sulfate aerosols tend to be less than 1 microm in diameter and tend to dominate the mass of this submicron size mode. The sulfur chemistry is dynamic, changing composition from predominantly sulfur dioxide and trioxide gasses near the volcano, to predominantly sulfate aerosols on the west side of the island. Time, concentration and composition characteristics of submicron aerosols and sulfur dioxide are described with respect to the related on-going health studies and public health management concerns. Exposures to sulfur dioxide and particulate matter equal to or less than 1 microm in size were almost always below the national ambient air quality standards (NAAQS). These standards do not however consider the acidic nature and submicron size of the aerosol, nor the possibility of the aerosol and the sulfur dioxide interacting in their toxicity. Time series plots, histograms and descriptive statistics of hourly averages give the reader a sense of some of the exposures observed.

Are remnant-like particles independent predictors of coronary heart disease incidence? The Honolulu Heart study.

BACKGROUND: Remnant-like particles have been proposed as a new risk factor for coronary heart disease (CHD). This is the first long-term prospective investigation of the relationship between remnant-like particles and a cardiovascular disease outcome in healthy men. METHODS AND RESULTS: A cohort of 1156 Japanese-American men aged 60 to 82 from the Honolulu Heart Program was followed for 17 years. During that period 164 incident cases of CHD were identified. In multivariate Cox regression analyses, baseline remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG) levels were significantly related to CHD incidence independently of nonlipid cardiovascular risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. Total triglyceride levels were an independent predictor of CHD incidence. However, in models including RLP and triglyceride level simultaneously, neither variable was significant when adjusted for the other. This finding can be attributed to the strong correlation between RLP-C and RLP-TG levels and total triglycerides. When individuals with normal triglyceride levels (n=894) were separated from those with elevated triglycerides (n=260), the association between RLPs and CHD relative risk was only significant for the group with elevated triglyceride levels. CONCLUSIONS: RLP levels predicted CHD incidence independently of nonlipid risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. However, RLP levels did not provide additional information about CHD incidence over and above total triglyceride levels. Therefore, this study does not support the need for testing of remnants in men if measures of fasting triglycerides are available.

Diabetes, insulin resistance, and dementia among HIV-1-infected patients.

OBJECTIVES: Metabolic complications have been associated with HIV-1 infection and with long-term use of antiretroviral (ARV) medications. In some studies, such complications have been linked to cardiovascular events, yet limited data exist concerning metabolic complications and dementia. The objective of this study was to examine the relationship between HIV-associated dementia (HAD) and diabetes among patients with HIV-1 infection. DESIGN: Cross-sectional analysis of entry data for a longitudinal cohort study. METHODS: A total of 203 participants who were enrolled in the Hawaii Aging with HIV Cohort between October 2001 and November 2003 served as the study population. Research case definitions of HAD were determined in consensus conferences by a panel that included neurologists, neuropsychologists, and a geriatrician. Diabetes was determined by self-report or a fasting glucose level > 125 mg/dL. RESULTS: Participants' ages ranged between 20-76 years at enrollment with approximately one-half aged >/=50 years. After adjustment for important covariates including age, education, ethnicity, CD4 lymphocyte count, duration of HIV infection, and protease inhibitor-based ARV therapy, we found a statistically significant association of diabetes with HAD (odds ratio 5.43, 1.66-17.70). A significant association remained after adjustment for other vascular risk factors. Among participants without diabetes, fasting glucose levels were higher with increasing impairment category. CONCLUSIONS: Within the Hawaii Aging with HIV Cohort, a longitudinal study enriched with older HIV-1-infected individuals, diabetes is associated with prevalent dementia. This finding is not fully explained by age or coexisting vascular risk factors. Evaluation of underlying mechanisms is warranted.

Ontogeny of arousal.

Ontogeny of arousal data constitute a vital supplement to the sparse literature on spontaneous neuronal activity. These data demonstrate that measurable infant spontaneous arousals (SAs) with an inherent oscillatory entrainment occur six times more in active sleep than in quiet sleep of the same duration and are identifiable as a human neurobiologic function. These SAs are not significantly associated with race or ethnicity, gender, total hours spent sleeping, percent time spent in active or quiet sleep, preterm status, history of a life-threatening event, having had a sibling who died of sudden infant death syndrome (SIDS), or having had a mother who smoked during this pregnancy. As measurable neurophysiologic events, SAs establish parameters for research at molecular and molar levels focusing on several critical areas: (1) the neuronal control of SA related to neurotransmitters, (2) as a significant antecedent factor in clinical cardiorespiratory events occurring in infants at high epidemiologic risk for SIDS; (3) as a regulatory biologic factor underlying temperament and executive cognitive functioning, and (4) morbidity and mortality effects possibly related to therapeutic interventions that alter SA levels.

Dairy intake is associated with lower body fat and soda intake with greater weight in adolescent girls.

Body fat and weight of 9- to 14-y-old girls (n = 323) from Kaiser Permanente were studied in relation to age, ethnicity, and physical activity. Mean age, calcium intake, weight, and iliac skinfold thickness were 11.5 +/- 1.4 y, 736.5 +/- 370.7 mg/d, 44.6 +/- 13.0 kg, and 12.4 +/- 6.1 mm, respectively. Multiple regression with age, ethnicity, height, Tanner breast stage, physical activity, energy, soda, and calcium intake explained 17% of the variation in iliac skinfold thickness. Calcium intake, age, and physical activity were significantly negatively associated with iliac skinfold thickness whereas height, Tanner breast stage, and Pacific Islander ethnicity were significantly positively associated (P < 0.0001, R(2) = 0.165). Substituting total calcium with dairy and nondairy calcium in separate models accounted for 16 and 15% of the variance, respectively (P < 0.0001, both models); 1 mg of total and dairy calcium was significantly associated with 0.0025 mm (P = 0.01) and 0.0026 mm (P = 0.02) lower iliac skinfold thickness. Thus, 1 milk serving was associated with 0.78 mm iliac skinfold thickness. The interaction of Asian ethnicity and dairy intake was significant (P = 0.027). Nondairy calcium was not associated with weight or iliac skinfold thickness. Soda intake was significantly positively associated with weight in both models (P = 0.01, both models). Decreasing soda and increasing dairy consumption among Asians may help maintain body fat and weight during adolescence.

Tree-structured supervised learning and the genetics of hypertension.

This paper is about an algorithm, FlexTree, for general supervised learning. It extends the binary tree-structured approach (Classification and Regression Trees, CART) although it differs greatly in its selection and combination of predictors. It is particularly applicable to assessing interactions: gene by gene and gene by environment as they bear on complex disease. One model for predisposition to complex disease involves many genes. Of them, most are pure noise; each of the values that is not the prevalent genotype for the minority of genes that contribute to the signal carries a "score." Scores add. Individuals with scores above an unknown threshold are predisposed to the disease. For the additive score problem and simulated data, FlexTree has cross-validated risk better than many cutting-edge technologies to which it was compared when small fractions of candidate genes carry the signal. For the model where only a precise list of aberrant genotypes is predisposing, there is not a systematic pattern of absolute superiority; however, overall, FlexTree seems better than the other technologies. We tried the algorithm on data from 563 Chinese women, 206 hypotensive, 357 hypertensive, with information on ethnicity, menopausal status, insulin-resistant status, and 21 loci. FlexTree and Logic Regression appear better than the others in terms of Bayes risk. However, the differences are not significant in the usual statistical sense.