GADGETS: a genetic algorithm for detecting epistasis using nuclear families.

Motivation: Epistasis may play an etiologic role in complex diseases, but research has been hindered because identification of interactions among sets of single nucleotide polymorphisms (SNPs) requires exploration of immense search spaces. Current approaches using nuclear families accommodate at most several hundred candidate SNPs.

Results: GADGETS detects epistatic SNP-sets by applying a genetic algorithm to case-parent or case-sibling data.

Family-Based Multi-SNP X Chromosome Analysis Using Parent Information.

We propose a method for association analysis of haplotypes on the X chromosome that offers both improved power and robustness to population stratification in studies of affected offspring and their parents if all three have been genotyped. The method makes use of assumed parental haplotype exchangeability (PHE), a weaker assumption than Hardy-Weinberg equilibrium (HWE). PHE requires that in the source population, of the three X chromosome haplotypes carried by the two parents, each is equally likely to be carried by the father.

A family-based, genome-wide association study of young-onset breast cancer: inherited variants and maternally mediated effects.

Young-onset breast cancer shows certain phenotypic and etiologic differences from older-onset breast cancer and may be influenced by some distinct genetic variants. Few genetic studies of breast cancer have targeted young women and no studies have examined whether maternal variants influence disease in their adult daughters through prenatal effects. We conducted a family-based, genome-wide association study of young-onset breast cancer (age at diagnosis <50 years).

Learning about the X from our parents.

The X chromosome is generally understudied in association studies, in part because the analyst has had limited methodological options. For nuclear-family-based association studies, most current methods extend the transmission disequilibrium test (TDT) to the X chromosome. We present a new method to study association in case-parent triads: the parent-informed likelihood ratio test for the X chromosome (PIX-LRT).

More extensive implementation of the chronic care model is associated with better lipid control in diabetes.

Objective: Chronic disease collaboratives help practices redesign care delivery. The North Carolina Improving Performance in Practice program provides coaches to guide implementation of 4 key practice changes: registries, planned care templates, protocols, and self-management support. Coaches rate progress using the Key Drivers Implementation Scales (KDIS).

Adrenomedullin signaling pathway polymorphisms and adverse pregnancy outcomes.

Objective: Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk.

Study Design: We genotyped 1,353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL).

Facilitators of transforming primary care: a look under the hood at practice leadership.

Purpose: This study examined how characteristics of practice leadership affect the change process in a statewide initiative to improve the quality of diabetes and asthma care.

Methods: We used a mixed methods approach, involving analyses of existing quality improvement data on 76 practices with at least 1 year of participation and focus groups with clinicians and staff in a 12-practice subsample. Existing data included monthly diabetes or asthma measures (clinical measures) and monthly practice implementation, leadership, and practice engagement scores rated by an external practice coach.

Maternal genotype and gestational diabetes.

Objective: To determine whether genetic variants associated with glucose homeostasis are associated with gestational diabetes (GDM).

Study Design: We genotyped 899 self-identified Caucasian women and 386 self-identified African-American women in the Pregnancy, Infection and Nutrition (PIN) Studies cohorts for 38 single-nucleotide polymorphisms (SNPs) associated with type II diabetes (T2DM) and/or glucose homeostasis in European populations.

Results: GDM was diagnosed in 56 of 899 (6.

Obesity and diabetes genetic variants associated with gestational weight gain.

Objective: We sought to determine whether genetic variants associated with diabetes and obesity predict gestational weight gain.

Study Design: A total of 960 participants in the Pregnancy, Infection, and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity.

Results: Among Caucasian and African American women (n = 960), KCNQ1 risk allele carriage was directly associated with weight gain (P < .

Pathways change in expression during replicative aging in Saccharomyces cerevisiae.

Yeast replicative aging is a process resembling replicative aging in mammalian cells. During aging, wild-type haploid yeast cells enlarge, become sterile, and undergo nucleolar enlargement and fragmentation; we sought gene expression changes during the time of these phenotypic changes. Gene expression studied via microarrays and quantitative real-time reverse-transcription polymerase chain reaction (qPCR) has shown reproducible, statistically significant changes in messenger RNA (mRNA) of genes at 12 and 18-20 generations.