Charles A. Weitz

Measures of autozygosity in decline: globalization, urbanization, and its implications for medical genetics.

This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so.

Morphological growth and thorax dimensions among Tibetan compared to Han children, adolescents and young adults born and raised at high altitude.

Summary. Background: Studies comparing the growth of indigenous high-altitude Aymara children and children of low-altitude European descent who have been born and raised at high altitude in the Andes have provided evidence for genetically-determined differences in thorax growth, as well as for population differences in height, weight and other measures of overall size. Comparable studies now can be undertaken in Asia because of the growing number of Han Chinese who have been born and raised at high altitude on the Qinghai–Tibetan Plateau. Aim: The study compares the growth of indigenous Tibetan children and children of Han descent who have been born and raised at the same high altitudes, and under similar socio-economic conditions. Subjects and methods: Measurements of stature, sitting height, weight, triceps and subscapular skinfolds, upper arm muscle area, transverse chest diameter, anterio-posterior chest diameter, and chest circumference were taken on 1439 Tibetan and Han males and females between the ages of 6 and 29 years who were born and raised 3200 m, 3800 m or at 4300 m in the high altitude province of Qinghai in western China. Results: Han–Tibetan differences in body size do not occur systematically for any measurement, for any age group, or for either gender; nor is there a systematic pattern of body size differences between 3200 m and 4300 m. This indicates that there are no differences in general growth between the two groups at high altitude in Qinghai, although both groups grow more slowly than urban children at low altitude in China. On the other hand, Tibetan males possess significantly deeper chests than Han males, and Tibetan females possess significantly wider chests than Han females. Tibetans of both sexes possess significantly larger chest circumferences than Han males and females. Conclusions: Although genetic similarities cannot be ruled out, comparable dietary stress is a likely explanation for the similar and slow morphological growth of Han and Tibetans at high altitude. However, Han–Tibetan differences in thorax dimensions are likely a consequence of population (genetic) differences in the response to hypoxia during growth.

Growth of Qinghai Tibetans living at three different high altitudes

This study compares the stature, weight, skinfolds, upper arm muscle area, and chest dimensions of Tibetan children, adolescents, and young adults who were born and raised, or who had lived from infancy, at 3,200 m, 3,800 m, and 4,300 m in Qinghai Province, Peoples Republic of China. While the individuals measured in Qinghai are among the tallest and heaviest Tibetans reported in the literature, they are nevertheless smaller and lighter than well-off children living at low altitude. The pattern of size variation among Tibetan males and females measured at the three high altitudes, along with evidence of a secular trend at 4,300 m, suggests that nutrition may significantly effect growth at high altitude. Only minor differences in thorax dimensions exist between Tibetan males and females measured at 3,200 m and 3,800 m. However, Tibetan males at 4,300 m possess slightly narrower and deeper chests (during and after adolescence) than males at 3,200 m and 3,800 m. Since individuals from 3,800 m and 4,300 m belong to the same local populations, this characteristic is unlikely to be genetically determined. However, it may be related to differences in the degree of hypoxia or to the influences of other environmental conditions.

Impact of modernization on adult body composition on five islands of varying economic development in vanuatu

The Republic of Vanuatu, similar to other South Pacific island nations, is undergoing a rapid health transition as a consequence of modernization. The pace of modernization is uneven across Vanuatus 63 inhabited islands, resulting in differential impacts on overall body composition and prevalence of obesity among islands, and between men and women. In this study, we investigated (1) how modernization impacts body composition between adult male and female Melanesians living on four islands of varying economic development in Vanuatu, and (2) how body composition differs between adult Melanesians and Polynesians living on rural islands in Vanuatu.

BLOOD PRESSURE AT REST AND DURING EXERCISE AMONG SHERPAS AND TIBETAN MIGRANTS IN NEPAL

Tibetan migrants living in an urban environment at low altitude show higher resting systolic blood pressures and more gradual increases in systolic blood pressure during exercise than do Tibetan migrants and Sherpas living at high altitude. Exercise differences are probably related to variations in activity pattern. Resting differences are probably not due to altitude or morphology; but are more likely associated with Western influences on diet and lifestyle.

Morphological growth of Han boys and girls born and raised near sea level and at high altitude in western China

This study compares the morphological characteristics of Han children, adolescents, and young adults who were born at 250 m near Beijing and at three high altitudes in Qinghai Province, Peoples Republic of China (3,200 m, 3,800 m, and 4,300 m). From ages 6 through 15, Han children growing up at high altitudes are significantly shorter, lighter, have less fat, and are less muscular than Han children growing up at low altitude. However, older adolescents and young adults show no such altitude differences. Younger adolescents and children in this study were all born after the government economic reforms of 1978. These reforms had a greater impact on the growth of children in and around large cities than on those in more remote areas. Therefore, the altitude differences in size among Han children ages 15 and younger may be a consequence of regional variation in health and nutrition, rather than due to the influence of hypoxia. There are no altitude‐related differences in thorax dimensions among Han children, adolescents, or young adults. This suggests that hypoxia does not affect the thorax growth of Han children. Am. J. Hum. Biol. 12:665–681, 2000.

Biocultural Adaptations of the High Altitude Sherpas of Nepal

There are a number of Tibetan-derived populations that inhabit the high altitude areas of the Nepal Himalayas. Collectively, they are referred to as Bhotias, which is from the Nepali word Bhot, meaning Tibet. Several of these groups are called Sherpas, a word derived from the Tibetan, Sharp-pa, meaning easterner. Perhaps the best-known group is the one living in the Khumbu region of eastern Nepal, which is adjacent to Mount Everest.

Larger FVC and FEV1 among Tibetans compared to Han born and raised at high altitude

OBJECTIVES This study compares forced vital capacity (FVC) and Forced Expiratory Volume at 1 Second (FEV1 ) of Tibetans with those of Han who were born and raised at high altitude. MATERIALS AND METHODS FVC and FEV1 tests were conducted among 1,063 children and adolescents between the ages of 6 and 20 years, and 184 adults between the ages of 21 and 39 years who had lived their entire lives at 3200 m, 3800 m and 4300 m in Qinghai Provence, Peoples Republic of China. RESULTS Even though FVC and FEV1 values of Han born and raised at high altitude are generally lower than those of Tibetans through age 15 in girls and age 16 in boys, differences are largely explained by variation in stature (height-squared) and chest circumference. Among older adolescents and adults, the FVC and FEV1 values of Tibetans are significantly larger than those of Han born and raised at high altitude; and are much larger than would be predicted, based on stature and chest circumference. DISCUSSION These results indicate that the large FVC and FEV1 values of Tibetan adults develop primarily from an accelerated pattern of lung growth that begins during mid-to-late adolescence and possibly extends into young adulthood. This developmental pattern is not only distinct from that of Han born and raised at high altitude, but also from those of Andean Quechua and Aymara. The pace of lung function growth may therefore represent another feature distinguishing the Tibetan from the Andean pattern of adaptation to high altitude hypoxia. Because of this, a search for features in the Tibetan genome related to this lung function growth phenotype might be productive and important.

Responses of Han Migrants Compared to Tibetans at High Altitude

While many studies have compared Tibetans and low‐altitude born Han living at high altitude, few have carefully controlled the chronological age at which lowlanders migrated, the length of time they had lived at high altitude, their nutrition, and their socio‐economic status. This has produced an array of results that frequently do not support the hypothesis that Tibetans and Han show fundamental differences in their response to hypoxia. Unlike the situation in the Andes, only one study has tested the developmental adaptation hypothesis on the Qinghai‐Tibetan plateau. This study shows that Tibetans and Han of the same age, who were born and raised in the same towns at the same altitudes, show considerable overlap in the individual distribution of [Hb], SaO2 and lung volumes. These results indicate that second‐generation Han make substantial developmental adjustments to hypoxia that are not reflected in studies of first‐generation migrants. Thus, there is a great need for further developmental studies to determine whether and/or how Han and Tibetan responses to hypoxia diverge, as well as for studies exploring whether Han and Tibetans who show similar responses also share genetic adaptations. Am. J. Hum. Biol. 25:169–178, 2013.

Modernization and the onset of overweight and obesity in bougainville and solomon islands children: Cross-sectional and longitudinal comparisons between 1966 and 1986

This set of cross-sectional and longitudinal data from children and young adults in certain Bougainville and Solomon Islands populations undergoing rapid modernization during the period 1966-1986 reveals very different responses to essentially the same stimuli-the introduction and widespread availability of western dietary items and reductions in habitual activity. Our analyses of over 2,000 children and young adults first measured in 1966-1972, with follow-up surveys in 1968-1970 and 1985-1986, show changes in overweight/obesity in these communities have their onset around puberty, and are not related to differences in childhood growth stunting. The prevalence of overweight and obesity increased substantially during the period of this study among young adults, particularly women, and in groups with more Polynesian affinities, where the frequency of overweight (BMI ≥ 25) tripled over this 20-year interval. However, the BMI of the more Papuan groups on Bougainville remained remarkably stable, even though they were close to the epicenter of modernization during this period, the Bougainville Copper Mine.