Genes for Good: Engaging the Public in Genetics Research via Social Media.

The Genes for Good study uses social media to engage a large, diverse participant pool in genetics research and education. Health history and daily tracking surveys are administered through a Facebook application, and participants who complete a minimum number of surveys are mailed a saliva sample kit ("spit kit") to collect DNA for genotyping. As of March 2019, we engaged >80,000 individuals, sent spit kits to >32,000 individuals who met minimum participation requirements, and collected >27,000 spit kits. Participants come from all 50 states and include a diversity of ancestral backgrounds. Rates of important chronic health indicators are consistent with those estimated for the general U.S. population using more traditional study designs. However, our sample is younger and contains a greater percentage of females than the general population. As one means of verifying data quality, we have replicated genome-wide association studies (GWASs) for exemplar traits, such as asthma, diabetes, body mass index (BMI), and pigmentation. The flexible framework of the web application makes it relatively simple to add new questionnaires and for other researchers to collaborate. We anticipate that the study sample will continue to grow and that future analyses may further capitalize on the strengths of the longitudinal data in combination with genetic information.

Proper conditional analysis in the presence of missing data: Application to large scale meta-analysis of tobacco use phenotypes.

Meta-analysis of genetic association studies increases sample size and the power for mapping complex traits. Existing methods are mostly developed for datasets without missing values, i.e. the summary association statistics are measured for all variants in contributing studies. In practice, genotype imputation is not always effective. This may be the case when targeted genotyping/sequencing assays are used or when the un-typed genetic variant is rare. Therefore, contributed summary statistics often contain missing values. Existing methods for imputing missing summary association statistics and using imputed values in meta-analysis, approximate conditional analysis, or simple strategies such as complete case analysis all have theoretical limitations. Applying these approaches can bias genetic effect estimates and lead to seriously inflated type-I or type-II errors in conditional analysis, which is a critical tool for identifying independently associated variants. To address this challenge and complement imputation methods, we developed a method to combine summary statistics across participating studies and consistently estimate joint effects, even when the contributed summary statistics contain large amounts of missing values. Based on this estimator, we proposed a score statistic called PCBS (partial correlation based score statistic) for conditional analysis of single-variant and gene-level associations. Through extensive analysis of simulated and real data, we showed that the new method produces well-calibrated type-I errors and is substantially more powerful than existing approaches. We applied the proposed approach to one of the largest meta-analyses to date for the cigarettes-per-day phenotype. Using the new method, we identified multiple novel independently associated variants at known loci for tobacco use, which were otherwise missed by alternative methods. Together, the phenotypic variance explained by these variants was 1.1%, improving that of previously reported associations by 71%. These findings illustrate the extent of locus allelic heterogeneity and can help pinpoint causal variants.

Association Analysis and Meta-Analysis of Multi-Allelic Variants for Large-Scale Sequence Data.

There is great interest in understanding the impact of rare variants in human diseases using large sequence datasets. In deep sequence datasets of >10,000 samples, ~10% of the variant sites are observed to be multi-allelic. Many of the multi-allelic variants have been shown to be functional and disease-relevant. Proper analysis of multi-allelic variants is critical to the success of a sequencing study, but existing methods do not properly handle multi-allelic variants and can produce highly misleading association results. We discuss practical issues and methods to encode multi-allelic sites, conduct single-variant and gene-level association analyses, and perform meta-analysis for multi-allelic variants. We evaluated these methods through extensive simulations and the study of a large meta-analysis of ~18,000 samples on the cigarettes-per-day phenotype. We showed that our joint modeling approach provided an unbiased estimate of genetic effects, greatly improved the power of single-variant association tests among methods that can properly estimate allele effects, and enhanced gene-level tests over existing approaches. Software packages implementing these methods are available online.

Water Footprint Allocation under Equity and Efficiency Considerations: A Case Study of the Yangtze River Economic Belt in China.

From a water footprint perspective, this paper adopts Gross Domestic Product (GDP) as the influencing factor to construct a lexicographical optimization framework for optimizing water resources allocation under equity and efficiency considerations. This approach consists of a lexicographic allocation of water footprints (LAWF) model and an input-output capacity of water footprints (IOWF) model. The proposed methodology is then applied to allocate water resources in the Yangtze River Economic Belt (YREB) by employing the 2013 cross-sectional data in the area. The results show that: (1) The LAWF scheme signifies reductions in water footprints in each of the YREB administrative units, thereby significantly strengthening their IOWFs. (2) IOWFs are affected by industrial attributes and natural endowments, and the impact tends to vary across different industries and regions. (3) Policy suggestions are proposed to effectively enhance the IOWFs of the weakest industries across the three YREB regions to exploit their natural endowments.

Medical Waste Disposal Method Selection Based on a Hierarchical Decision Model with Intuitionistic Fuzzy Relations.

Although medical waste usually accounts for a small fraction of urban municipal waste, its proper disposal has been a challenging issue as it often contains infectious, radioactive, or hazardous waste. This article proposes a two-level hierarchical multicriteria decision model to address medical waste disposal method selection (MWDMS), where disposal methods are assessed against different criteria as intuitionistic fuzzy preference relations and criteria weights are furnished as real values. This paper first introduces new operations for a special class of intuitionistic fuzzy values, whose membership and non-membership information is cross ratio based ]0, 1[-values. New score and accuracy functions are defined in order to develop a comparison approach for ]0, 1[-valued intuitionistic fuzzy numbers. A weighted geometric operator is then put forward to aggregate a collection of ]0, 1[-valued intuitionistic fuzzy values. Similar to Saaty's 1-9 scale, this paper proposes a cross-ratio-based bipolar 0.1-0.9 scale to characterize pairwise comparison results. Subsequently, a two-level hierarchical structure is formulated to handle multicriteria decision problems with intuitionistic preference relations. Finally, the proposed decision framework is applied to MWDMS to illustrate its feasibility and effectiveness.