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Presented is a program for the undergraduate mathematical preparation for work in computer science. Discussed are three types of courses: (1) mathematics courses of a general nature, which should be available for the prospective specialist in Computer Science, (2) technical courses in Computer Science, most of which will generally be taught outside the mathematics department, and (3) laboratory courses in Computer Science designed to acquaint the student with the scope and power of a high speed computer and with some of the techniques by which its potential can be realized. Separate programs for mathematics and for non-mathematics majors who plan to enter the field of computing are described. (RP)

Reported is an initial attempt to define a minimal college mathematics library. Included is a list of some 300 books, from which approximately 170 are to be chosen to form a basic library in undergraduate mathematics. The areas provided for in this list include Algebra, Analysis, Applied Mathematics, Geometry, Topology, Logic, Foundations and Set Theory, Probability-Statistics, and Number Theory. The intended goals of this basic collection are to (1) provide the student with introductory materials in various fields of mathematics which he may not have previously encountered, (2) provide the interested students with reading material collateral to his course work, (3) provide the student with reading at a level beyond that ordinarily encountered in the undergraduate curriculum, (4) provide the faculty with reference material, and (5) provide the general reader with elementary material in the field of mathematics. (RP)

THIS REPORT DESCRIBES A PROGRAM FOR THE UNDERGRADUATE MATHEMATICAL PREPARATION OF STUDENTS IN THE BIOLOGICAL, MANAGEMENT, AND SOCIAL SCIENCES (BMSS). THE COMMITTEE RECOMMENDS A SEQUENCE OF COURSES WHICH IS DESIGNED TO PROVIDE VARIED TRAINING IN MATHEMATICS IN THE LIMITED TIME BMSS STUDENTS HAVE AVAILABLE. OF SPECIAL IMPORTANCE ARE ELEMENTARY ANALYSIS, PROBABILITY AND STATISTICS, AND LINEAR ALGEBRA. THE PRINCIPAL IDEAS UNDERLYING THE SEQUENCE FOR BMSS STUDENTS ARE (1) MATHEMATICS IS NEEDED PRIMARILY AS A LANGUAGE FOR SCIENTIFIC REASONING, (2) BMSS STUDENTS DO NOT NEED AS MUCH TRAINING IN DETAILED TECHNIQUES AS DO MATHEMATICS AND PHYSICAL SCIENCE STUDENTS, (3) IT IS UNREASONABLE TO EXPEND AS MUCH TIME ON RIGOROUS PROOFS FOR BMSS STUDENTS AS FOR MATHEMATICS MAJORS, AND (4) MORE STRESS SHOULD BE PLACED ON APPLICATIONS WHICH ARE OF SPECIAL INTEREST IN THE BIOLOGICAL AND SOCIAL SCIENCES. THE RECOMMENDATIONS OF THE COMMITTEE FALL INTO THREE PARTS--(1) A BASIC FOUR-COURSE, TWO-YEAR SEQUENCE FOR BMSS STUDENTS, (2) A TWO-COURSE PROBABILITY AND STATISTICS SEQUENCE, AND (3) SOME ADVANCED COURSES THAT SERVE AS ELECTIVES. THE COMMITTEE ON THE UNDERGRADUATE PROGRAM IN MATHEMATICS IS CONVINCED THAT THE REQUIREMENT OF SIX COURSES--THE BASIC SEQUENCE PLUS THE PROBABILITY AND STATISTICS SEQUENCE--IS MINIMAL FOR FUTURE GRADUATE STUDENTS IN THE BMSS AREAS. THIS DOCUMENT IS ALSO AVAILABLE WITHOUT CHARGE FROM CUPM CENTRAL OFFICE, P. O. BOX 1024, BERKELEY, CALIFORNIA 94701. (RP)

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.

Genome-wide association (GWA) studies have identified multiple new genomic loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)1-11. Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to discover loci at which common alleles have modest effects, we performed meta-analysis of three T2D GWA scans encompassing 10,128 individuals of European-descent and ~2.2 million SNPs (directly genotyped and imputed). Replication testing was performed in an independent sample with an effective sample size of up to 53,975. At least six new loci with robust evidence for association were detected, including the JAZF1 (p=5.0×10−14), CDC123/CAMK1D (p=1.2×10−10), TSPAN8/LGR5 (p=1.1×10−9), THADA (p=1.1×10−9), ADAMTS9 (p=1.2×10−8), and NOTCH2 (p=4.1×10−8) gene regions. The large number of loci with relatively small effects indicates the value of large discovery and follow-up samples in identifying additional clues about the inherited basis of T2D.

Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 × 10–7). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 × 10–26, and combining results from all studies resulted in an overall P value for association of 6.4 × 10–33. Across these studies, fasting glucose concentrations increased 0.01–0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.