@article {6633, title = {Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.}, journal = {Diabetes}, volume = {61}, year = {2012}, month = {2012 Jun}, pages = {1642-7}, abstract = {

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69\% in American Indians to 100\% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.

}, keywords = {Adult, Aged, Aged, 80 and over, Alleles, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Metagenomics, Middle Aged, Population Groups, Risk, Risk Factors}, issn = {1939-327X}, doi = {10.2337/db11-1296}, author = {Haiman, Christopher A and Fesinmeyer, Megan D and Spencer, Kylee L and B{\r u}zkov{\'a}, Petra and Voruganti, V Saroja and Wan, Peggy and Haessler, Jeff and Franceschini, Nora and Monroe, Kristine R and Howard, Barbara V and Jackson, Rebecca D and Florez, Jose C and Kolonel, Laurence N and Buyske, Steven and Goodloe, Robert J and Liu, Simin and Manson, JoAnn E and Meigs, James B and Waters, Kevin and Mukamal, Kenneth J and Pendergrass, Sarah A and Shrader, Peter and Wilkens, Lynne R and Hindorff, Lucia A and Ambite, Jose Luis and North, Kari E and Peters, Ulrike and Crawford, Dana C and Le Marchand, Lo{\"\i}c and Pankow, James S} } @article {1620, title = {Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.}, journal = {J Clin Psychopharmacol}, volume = {33}, year = {2013}, month = {2013 Apr}, pages = {206-10}, chapter = {206}, abstract = {

Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 {\texttimes} 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 {\texttimes} 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 {\texttimes} 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.

}, keywords = {Aged, Alcohol Drinking, Alcoholism, Case-Control Studies, European Continental Ancestry Group, Feasibility Studies, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk}, issn = {1533-712X}, doi = {10.1097/JCP.0b013e318287009a}, author = {Hamidovic, Ajna and Goodloe, Robert J and Young, Taylor R and Styn, Mindi A and Mukamal, Kenneth J and Choquet, Helene and Kasberger, Jay L and Buxbaum, Sarah G and Papanicolaou, George J and White, Wendy and Volcik, Kelly and Spring, Bonnie and Hitsman, Brian and Levy, Daniel and Jorgenson, Eric} } @article {6292, title = {No evidence of interaction between known lipid-associated genetic variants and smoking in the multi-ethnic PAGE population.}, journal = {Hum Genet}, volume = {132}, year = {2013}, month = {2013 Dec}, pages = {1427-31}, abstract = {

Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype-phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Architecture Using Genomics and Epidemiology (PAGE) study. Despite their biological plausibility, we were unable to detect significant SNP {\texttimes} smoking interactions.

}, keywords = {Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Ethnic Groups, Female, Gene Frequency, Gene-Environment Interaction, Genetics, Population, Genome-Wide Association Study, Humans, Lipid Metabolism, Male, Polymorphism, Single Nucleotide, Prevalence, Smoking, Triglycerides, Young Adult}, issn = {1432-1203}, doi = {10.1007/s00439-013-1375-3}, author = {Dumitrescu, Logan and Carty, Cara L and Franceschini, Nora and Hindorff, Lucia A and Cole, Shelley A and B{\r u}zkov{\'a}, Petra and Schumacher, Fredrick R and Eaton, Charles B and Goodloe, Robert J and Duggan, David J and Haessler, Jeff and Cochran, Barbara and Henderson, Brian E and Cheng, Iona and Johnson, Karen C and Carlson, Chris S and Love, Shelly-Anne and Brown-Gentry, Kristin and Nato, Alejandro Q and Quibrera, Miguel and Shohet, Ralph V and Ambite, Jose Luis and Wilkens, Lynne R and Le Marchand, Lo{\"\i}c and Haiman, Christopher A and Buyske, Steven and Kooperberg, Charles and North, Kari E and Fornage, Myriam and Crawford, Dana C} } @article {6111, title = {Post-genome-wide association study challenges for lipid traits: describing age as a modifier of gene-lipid associations in the Population Architecture using Genomics and Epidemiology (PAGE) study.}, journal = {Ann Hum Genet}, volume = {77}, year = {2013}, month = {2013 Sep}, pages = {416-25}, abstract = {

Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age-dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or >=50 years of age; females: pre- or postmenopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age-specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet < 0.05). The association between rs174547 (FADS1) and LDL-C in males displayed the most evidence for heterogeneity between age groups (Phet = 1.74E-03, I(2) = 89.8), with a significant association in older males (P = 1.39E-06) but not younger males (P = 0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP-trait associations despite large sample sizes.

}, keywords = {Adult, Aged, European Continental Ancestry Group, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Lipids, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Risk Factors}, issn = {1469-1809}, doi = {10.1111/ahg.12027}, author = {Dumitrescu, Logan and Carty, Cara L and Franceschini, Nora and Hindorff, Lucia A and Cole, Shelley A and B{\r u}zkov{\'a}, Petra and Schumacher, Fredrick R and Eaton, Charles B and Goodloe, Robert J and Duggan, David J and Haessler, Jeff and Cochran, Barbara and Henderson, Brian E and Cheng, Iona and Johnson, Karen C and Carlson, Chris S and Love, Shelly-Ann and Brown-Gentry, Kristin and Nato, Alejandro Q and Quibrera, Miguel and Anderson, Garnet and Shohet, Ralph V and Ambite, Jose Luis and Wilkens, Lynne R and Marchand, Loic Le and Haiman, Christopher A and Buyske, Steven and Kooperberg, Charles and North, Kari E and Fornage, Myriam and Crawford, Dana C} }