Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.

X‐linked Charcot‐Marie‐Tooth disease (CMTX) is the second most common form of Charcot‐Marie‐Tooth disease. Variable histopathological and nerve conduction velocity (NCV) results have suggested either a primary demyelinating or axonal polyneuropathy. We identified five individuals across three generations in a family with CMTX associated with a mutation in the gene coding for connexin 32. All individuals were studied by clinical neurological examination, DNA analysis, and nerve conduction studies. The proband (1174/KD) also underwent a sural nerve biopsy. As expected, all the affected males were more clinically affected than the females. All affected males and obligate female carriers exhibited some electrophysiological characteristics of demyelination. However, striking heterogeneity of nerve conduction velocities was seen. This family shows that CMTX is a heterogeneous and distinctly nonuniform demyelinating polyneuropathy, the severity of which varies with sex and age. Such electrophysiological variability is unique among hereditary neuropathies. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 182–188, 2000.

Substantially more women than men develop multiple sclerosis (MS), but information about the effects of MS and gender-specific issues such as pregnancy, breastfeeding, menstruation and hormone use is lacking. A survey study of neurologists' practice patterns was undertaken to elicit information about gender-specific topics and the use of disease-modifying MS therapies (DMT) including the interferons and glatiramer acetate (GA). A total of 147 surveys were returned. Half of respondents require patients to discontinue DMT during pregnancy, while 35% encourage discontinuation. Among those who allow patients to continue therapy, half consider GA to be safer during pregnancy than the interferons. Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among the 11% who actually prescribe during breastfeeding, most recommend GA. Neurologists generally leave the decision to breastfeed up to patients, and most refer patients to obstetrician/gynaecologists for counselling about contraception or hormone replacement therapy. The survey results described here provide insight into how neurologists manage reproductive health issues among women with MS.

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