Helen Lyon

On the adjustment for covariates in genetic association analysis: a novel, simple principle to infer direct causal effects

In genetic association studies, different complex phenotypes are often associated with the same marker. Such associations can be indicative of pleiotropy (i.e. common genetic causes), of indirect genetic effects via one of these phenotypes, or can be solely attributable to non‐genetic/environmental links between the traits. To identify the phenotypes with the inducing genetic association, statistical methodology is needed that is able to distinguish between the different causes of the genetic associations. Here, we propose a simple, general adjustment principle that can be incorporated into many standard genetic association tests which are then able to infer whether an SNP has a direct biological influence on a given trait other than through the SNPs influence on another correlated phenotype. Using simulation studies, we show that, in the presence of a non‐marker related link between phenotypes, standard association tests without the proposed adjustment can be biased. In contrast to that, the proposed methodology remains unbiased. Its achieved power levels are identical to those of standard adjustment methods, making the adjustment principle universally applicable in genetic association studies. The principle is illustrated by an application to three genome‐wide association analyses. Genet. Epidemiol. 33:394–405, 2009.

Obesity and diabetes genetic variants associated with gestational weight gain

OBJECTIVEnWe sought to determine whether genetic variants associated with diabetes and obesity predict gestational weight gain.nnnSTUDY DESIGNnA total of 960 participants in the Pregnancy, Infection, and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity.nnnRESULTSnAmong Caucasian and African American women (n = 960), KCNQ1 risk allele carriage was directly associated with weight gain (P < .01). In Bayesian hierarchical models among Caucasian women (n = 628), we found posterior odds ratios >3 for inclusion of TCF2 and THADA SNPs in our models. Among African American women (n = 332), we found associations between risk allele carriage and weight gain for the THADA and INSIG2 SNPs. In Bayesian variable selection models, we found an interaction between the TSPAN8 risk allele and pregravid obesity, with lower weight gain among obese risk allele carriers.nnnCONCLUSIONnWe found evidence that diabetes and obesity risk alleles interact with maternal pregravid body mass index to predict gestational weight gain.

Standardization of reagents and methods used in cytological and histological practice with emphasis on dyes, stains and chromogenic reagents

SummaryThe need for the standardization of reagents and methods used in the histology laboratory is demonstrated. After definitions of dyes, stains, and chromogenic reagents, existing standards and standards organizations are discussed. This is followed by practical instructions on how to standardize dyes and stains through the preparation of reference materials and the development of chromatographic methods. An overview is presented of the problems concerned with standardization of the Romanowsky-Giemsa stain for cytological and histological application. Finally, the problem of how to convince routine dye and stain users of the need for standardization in their histology laboratories is discussed.