Live birth sex ratios and father's geographic origins in Jerusalem, 1964-1976.

OBJECTIVE: To examine whether ancestry influenced sex ratios of offspring in a birth cohort before parental antenatal sex selection influenced offspring sex. METHODS: We measured the sex ratio as the percent of males according to countries of birth of paternal and maternal grandfathers in 91,459 live births from 1964 to 1976 in the Jerusalem Perinatal Study. Confidence limits (CI) were computed based on an expected sex ratio of 1.05, which is 51.4% male. RESULTS: Of all live births recorded, 51.4% were male. Relative to Jewish ancestry (51.4% males), significantly more males (1,761) were born to Muslim ancestry (54.5, 95% CI = 52.1-56.8, P = 0.01). Among the former, sex ratios were not significantly associated with paternal or maternal age, education, or offspring's birth order. Consistent with a preference for male offspring, the sex ratio decreased despite increasing numbers of births over the 13-year period. Sex ratios were not affected by maternal or paternal origins in North Africa or Europe. However, the offspring whose paternal grandfathers were born in Western Asia included fewer males than expected (50.7, 50.1-51.3, P = 0.02), whether the father was born abroad (50.7) or in Israel (50.8). This was observed for descendents of paternal grandfathers born in Lebanon (47.6), Turkey (49.9), Yemen & Aden (50.2), Iraq (50.5), Afghanistan (50.5), Syria (50.6), and Cyprus (50.7); but not for those from India (51.5) or Iran (51.9). The West Asian group showed the strongest decline in sex ratios with increasing paternal family size. CONCLUSIONS: A decreased sex ratio associated with ancestry in Western Asia is consistent with reduced ability to bear sons by a subset of Jewish men in the Jerusalem cohort. Lower sex ratios may be because of pregnancy stress, which may be higher in this subgroup. Alternatively, a degrading Y chromosome haplogroup or other genetic or epigenetic differences on male germ lines could affect birth ratios, such as differential exposure to an environmental agent, dietary differences, or stress. Differential stopping behaviors that favor additional pregnancies following the birth of a daughter might exacerbate these lower sex ratios.

Growth and schizophrenia: aetiology, epidemiology and epigenetics.

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, since advancing paternal age is the major source of new mutations in humans. We found that paternal age at conception is a robust risk factor for schizophrenia, explaining perhaps a quarter of all cases. The predisposing genetic events appear to occur stochastically in proportion to advancing paternal age, and the possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The risk might also be related to paternal toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes or other factors that influence the fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germline cause an independent and common variant of schizophrenia and that abnormal methylation of paternally imprinted genes could be the mechanism. These findings suggest exciting new directions for research into the aetiology of schizophrenia.

Abnormal phospholipid metabolism in schizophrenia: evidence from epidemiological findings, clinical observations, and preliminary clinical trials.

Both epidemiological findings and clinical observations and have shaped our thinking as regards to the neuropathology of schizophrenia. Epidemiological findings implicating environmental risk factors, including maternal dietary deficiency and urban birth place, suggest schizophrenia is a developmental disorder, whereas clinical observations gave rise to the "dopamine hypothesis." Epidemiological findings lead to complex multifactorial models, while clinical observations lead to more readily to testable, but not necessarily generalizable, hypotheses. Points where findings from these different approaches converge may provide us with new insights and points of departure. In this paper, clinical observations and epidemiological findings are presented which suggests that a subgroup of schizophrenics have abnormalities in phospholipid metabolism. Preliminary clinical trials involving administration of omega-3 fatty acids thus far appear to support this hypothesis.

Electromagnetic field exposure induces rapid, transitory heat shock factor activation in human cells.

Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal growth temperatures results in heat shock factor 1 activation and heat shock element binding, a sequence of events that mediates the stress-induced transcription of the stress gene HSP70 and increased synthesis of the stress response protein hsp70kD. Thus, the events mediating the electromagnetic field-stimulated stress response appear to be similar to those reported for other physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) and could well be the general mechanism of interaction of electromagnetic fields with cells.