Reproductive behavior and health in consanguineous marriages

In many regions of Asia and Africa, consanguineous marriages currently account for approximately 20 to 50% of all unions, and preliminary observations indicate that migrants from these areas continue to contract marriages with close relatives when resident in North America and Western Europe. Consanguinity is associated with increased gross fertility, due at least in part to younger maternal age at first livebirth. Morbidity and mortality also may be elevated, resulting in comparable numbers of surviving offspring in consanguineous and nonconsanguineous families. With advances in medicine and public health, genetic disorders will account for an increased proportion of disease worldwide. Predictably, this burden will fall more heavily on countries and communities in which consanguinity is strongly favored, as the result of the expression of deleterious recessive genes. However, studies conducted in such populations indicate that the adverse effects associated with inbreeding are experienced by a minority of families.

Variation at Diabetes- and Obesity-Associated Loci May Mirror Neutral Patterns of Human Population Diversity and Diabetes Prevalence in India

South Asian populations harbor a high degree of genetic diversity, due in part to demographic history. Two studies on genome-wide variation in Indian populations have shown that most Indian populations show varying degrees of admixture between ancestral north Indian and ancestral south Indian components. As a result of this structure, genetic variation in India appears to follow a geographic cline. Similarly, Indian populations seem to show detectable differences in diabetes and obesity prevalence between different geographic regions of the country. We tested the hypothesis that genetic variation at diabetes-and obesity-associated loci may be potentially related to different genetic ancestries. We genotyped 2977 individuals from 61 populations across India for 18 SNPs in genes implicated in T2D and obesity. We examined patterns of variation in allele frequency across different geographical gradients and considered state of origin and language affiliation. Our results show that most of the 18 SNPs show no significant correlation with latitude, the geographic cline reported in previous studies, or by language family. Exceptions include KCNQ1 with latitude and THADA and JAK1 with language, which suggests that genetic variation at previously ascertained diabetes-associated loci may only partly mirror geographic patterns of genome-wide diversity in Indian populations.

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.