Supplemental materials published online only (at http://www.circulationaha.org)
Online Table I. Genome scan results for IR-related traits in Hispanic Hypertension Families
chromosome / BMI / ginf_bsa / homa / Fasting insulin /Leptin
/ SBP / DBP / MAPHeritability / 0.71 / 0.47 / 0.32 / 0.48 / 0.52 / 0.64 / 0.34 / 0.52
1 / 2.31 / 1.62 / 0.45 / 0.39 / 0.83 / 2.48 / 0.87 / 1.89
cM / 242 / 237 / 0 / 110 / 60 / 7 / 114 / 4
2 / 1.5 / 0.69 / 0.83 / 0.91 / 1.47 / 1.57 / 1.7 / 1.64
186 / 114 / 173 / 172 / 182 / 242 / 223 / 232
3 / 0.33 / 0.68 / 1.04 / 1.15 / 1.04 / 0.59 / 0.64 / 0.67
60 / 215 / 67 / 69 / 138 / 125 / 92 / 124
4 / 0.13 / 1.35 / 0.7 / 0.67 / 0.9 / 0.96 / 0.82 / 1.59
40 / 33 / 158 / 11 / 42 / 34 / 37 / 35
5 / 0.62 / 0.38 / 0.4 / 0.96 / 1.1 / 0.39 / 0.8 / 0.66
192 / 175 / 160 / 191 / 182 / 40 / 183 / 117
6 / 0.93 / 1.19 / 0.41 / 0.2 / 1.44 / 1.12 / 0.38 / 0.54
103 / 152 / 10 / 25 / 182 / 129 / 130 / 130
7 / 0.75 / 1.83 / 1.86 / 3.36 / 2.1 / 2.06 / 0.51 / 1.39
141 / 72 / 128 / 128 / 140 / 120 / 115 / 115
8 / 0.16 / 0.65 / 1.15 / 0.95 / 0.83 / 0.48 / 0.19 / 0.33
160 / 151 / 28 / 150 / 164 / 95 / 65 / 100
9 / 1.37 / 0.4 / 1.92 / 0.44 / 1.85 / 0.5 / 1.05 / 1.01
23 / 55 / 14 / 5 / 24 / 55 / 126 / 136
10 / 2.1 / 0.37 / 0.78 / 0.8 / 0.14 / 0.13 / 0.47 / 0.28
117 / 20 / 117 / 117 / 165 / 5 / 145 / 150
11 / 0.69 / 0.79 / 0.5 / 1.21 / 0.4 / 0.82 / 0.71 / 0.84
43 / 140 / 0 / 0 / 135 / 132 / 148 / 146
12 / 0.51 / 0.28 / 0.51 / 1.39 / 1.19 / 0.74 / 0.39 / 0.66
25 / 95 / 150 / 148 / 17 / 108 / 105 / 108
13 / 1.01 / 1.13 / 0.4 / 0.26 / 0.56 / 0.59 / 0.52 / 0.49
33 / 20 / 65 / 70 / 95 / 30 / 50 / 35
14 / 0.4 / 0.55 / 0.77 / 0.47 / 0.81 / 0.39 / 0.19 / 0.32
40 / 50 / 41 / 75 / 96 / 20 / 30 / 30
15 / 0.26 / 0.53 / 0.01 / 1.45 / 2.23 / 0.6 / 0.79 / 0.85
20 / 0 / 30 / 74 / 20 / 115 / 116 / 117
16 / 0.77 / 0.39 / 0.4 / 1.77 / 1.05 / 1.01 / 0.49 / 0.57
29 / 60 / 35 / 68 / 51 / 63 / 60 / 60
17 / 0.54 / 0.07 / 1.66 / 0.4 / 0.25 / 0.25 / 0.23 / 0.35
45 / 80 / 93 / 100 / 125 / 115 / 125 / 125
18 / 0.18 / 0.33 / 1.58 / 0.54 / 0.07 / 0.72 / 0.32 / 0.6
10 / 5 / 107 / 55 / 115 / 0 / 10 / 10
19 / 0 / 0.01 / 0.17 / 0.24 / 0 / 0.01 / 0.04 / 0.02
0 / 35 / 100 / 20 / 50 / 20 / 20 / 20
20 / 0.54 / 0.34 / 0.5 / 0.28 / 0.87 / 0 / 0.39 / 0.19
10 / 0 / 0 / 5 / 9 / 0 / 0 / 0
21 / 0.01 / 0.43 / 0.28 / 0.65 / 0.11 / 1.15 / 0.74 / 1.11
25 / 0 / 30 / 54 / 35 / 37 / 40 / 39
22 / 1.06 / 0.08 / 0.04 / 0.14 / 0.73 / 0.23 / 0.07 / 0.14
3 / 35 / 0 / 0 / 0 / 0 / 0 / 0
Online Table II. Review of Genome Scan Studies for BP/Hypertension, Type II DM, and Obesity.
First author / Journal / ascertainment trait / Population (study) / Sample size / Trait / Location(centiMorgan, cM) / Lod Score / Method
Hypertension/Blood Pressure
Atwood LD / Hypert, 2001 / CAD, screen / MA, SAFHS / 10 Family (444 Individuals) / PP (=SBP-DBP) / 21,37/D21S1440
7,114/D7S1799
D8S1100
18,116/D18S844 / 2.78
2.04
1.98
1.95 / SOLAR
Zhu DL / J Hypert,2001 / Chinese / 283 ASP (stage I)
637 ASP (stage II)
777 ASP (stage III) / HTN / Stage I
2, 27/D2S168
2,152/D2S151
2, 161/D2S142
Stage II
D2S151
D2S142
Stage III
2, 161/D2S142 / Suggestive
Significant
Significant
2.24 / GHP
Hsueh WC / Circulation, 2000 / NIDDM / Old Order Amish / 28 pedigrees (694 individuals), 436 parent-offspring, 1326 sibpairs, 1342 avuncular,
1311 cousin / SBP
DBP / 2,220/D2S326
2,210/D2S117 / 1.64
3.36 / SOLAR
Levy D / Hypert, 2000 / Healthy / Framingham Heart / 322 families (1702 individuals) / Longitudinal
Mean SBP
Mean SBP
Mean DBP
Mean DBP / 17, 67/ATC6A06
17, 94
17,74
18, 7 / 4.7
2.2
2.1
2.1 / SOLAR
Pankow JS / Hypert, 2000 / HTN / White, HyperGEN / 498 sib-pairs / Postural change
SBP
SBP
DBP / 18,.80(D18S858)
6p
6p / 2.6
1.9
1.7 / SOLAR
Perola M / J Hypert, 2000 / HTN / Caucasian (Finland) / 47 Family, twin / HTN / AT1
2q
22q
xp / 4.04
2.96
2.07
2.41
Rice T / Circulation, 2000 / Random & obese / Quebec / 206 (125 Random, 81 obese) family;335 sibpairs (226 random, 109 obese) / SBP / 1,98/D1S551
2,97/D2S1790
2,103/D2S2972
5,32/D5S1986
7,135/D7S530
8,87/8q(CRH)
19,4/D19S247 / 1.75
2.28
2.44
2.80
2.26
2.11
2.10 / SEGPATH;
MAPMAKER/SIB
Sharma P / Hypert, 2000 / HTN / Caucasian / 169 sibpairs (first stage)
? sibpairs (second pass) / HTN / D11S934
Chr 11 / 1.72
Not Significant / GH
Krushkal J / Circulation, 1999 / Random / White,
GENOA / 55, 69 discordant sibpairs / SBP / 6,143/D6S1009
15,97/D15S652
5,189/D5S1471
2,57/D2S1788 / P<0.0001
0.0033
0.0076
0.0089 / T statistics (Risch & Zhang)
Xu X / AJHG,1999 / Random / Chinese / 564 sibpairs
(207 discordant, 258 high concordant, 99 low concordant) / SBP
SBP
SBP
DBP
DBP
SBP
Both
DBP
Both
?
DBP / D11S2019
17,24/D17S1303
3,6/D3S2387
16,64/D16S3396 15,105/D15S657
4,73/D4S3248
7,155/D7S2195
10,46/D10S1423
20,39/D20S470
20,12/D20S482
21,25/D21S2052 / 2.07
2.16
2.03
2.74
2.69
2.38
?
2.33
1.98
?
2.20 / ASPEX
GENEHUNTER
Insulin Resistance
Mitchell BD / Diabetes, 2000 / Pop-based screen / MA, SAFHS / 10 pedigree (391 individuals) / Fasting insulin / 3,100/D3S1600 / 3.07 / SOLAR
Watanabe RM / AJHG, 2000 / NIDDM / Caucasian, FUSION / 719 sibpairs, 210nuclear families / C-peptide/glucose
C-peptide
C-peptide
C-peptide/glucose
Insulin
Insulin
Insulin/glucose
BMI
Insulin
Insulin resistance
Insulin resistance / 3,53
3,58
7,75
7,75
7,101
11,89
11,91
13,7
14,102
17,0
19,74 / 3.13
2.26
1.63
1.76
1.94
2.07
2.32
2.95
2.67
1.54
1.82 / USERFQTL
Pratley RE / JCI, 1998 / Non-diabetic, Screen / Pima Indians / 109 nuclear (388 sibpairs) / Fasting insulin
2-h insulin
2-h insulin
fasting insulin
fasting glucose / 3,153/D3S1764
3,8/D3S1744
9,96/D9S938
4,59/D4S2629
22,36/D22S683 / 1.5-1.7
2.31
1.94
1.15
3.15 / GH
Duggirala R / AJHG, 1996 / NIDDM / MA, SAFADS / 32 family (579 individuals), 620sibpairs / Proinsulin
Skinfolds / 7,136/D7S530 7,133/D7S514 / 3.0
4.2 / SOLAR
Type II Diabetes
Ghosh S / AJHG, 2000 / NIDDM / Finish, FUSION / 719 sibpairs / NIDDM / 20, 69/D20S88620,56/D20S107
20,17.5/D20S892
11, 84/D11S901
2, 5.5/D2S319
10, 75/D10S1652
6, 112.5/D6S287 / 2.15
2.04
1.99
1.75
0.87
0.77
0.61 / SIBLINK
Elbein SC / Diabetes, 1999 / NIDDM / Caucasian / 42 pedigrees / NIDDM / 1,214
1,204/CRP / 2.3
4.3 / GHP
GH(recessive)
Hanson RL / AJHG, 1998 / Pop-based screen / Pima Indians / 264 nuclear (966 siblings) / DM&BMI
DM
DM / 11,140/D11S912
1,192/D1S2127
7,114/D7S1799 / 5.43
3.65
0.70 / MAPMAKER/SIBS
Complications of Hypertension
DeWan AT / AJHG, 2001 / HTN / Africa & White, HyperGEN / 215 (Africa), 265 (White) ASP / Kidney function
(creatinine clearance) / 3,215/D3S2398
3,58/D3S2432
3,115/D3S4529 / 3.61 (Africa)
2.50 (Africa)
3.36 (White) / GH2
Imperatore G / Diabetes, 1998 / NIDDM / Pima Indians / 98 ASP (nephropathy)
103 ASP (retinopathy) / Nephropathy
Retinopathy / 3,181/D3S1763
7,144/D7S1804
20,18/D20S473
9,89/D9S1120 / 1.48
2.04
1.83
1.46 / GH;simulation
Obesity—BMI/Leptin/Body Fat
Kissebah AH / PNAS, 2000 / Obesity, screen / CaucasianTOPS / 507 nuclear family
(2209 individuals), 5399 pairs / BMI
Waist
HIP
Weight
Insulin
Leptin / 3, 190/D3S2407
3, 190
3, 189
3, 189
3, 202/D3S2398
17,38/D17S947 / 3.3
2.40
3.54
3.17
3.01
4.97 / SOLAR
Ohman M / J Clin Endo & Metab, 2000 / Obesity / Finnish / 100 ASP (stage I)
+93 ASP (stage II) / Obesity / 18,99
x,120
x,115/DxS6804 / 2.16
2.10
3.5 / GH;ANALYZE
Van der Kallen CJ / Int J Obes Rela Metab Disord, 2000 / FCH / Caucasian / 19 pedigrees (198individuals) / Leptin
BMI
TNFRSF1A
BMI / 1,89/D1S3728
1,89/D1S3728
D8S1110
10q/AFM198ZB / 3.4
1.2
2.8
3.3 / GH
Mitchell BD / Diabetes, 1999 / Pop-based screen / MA
SAFHS / 10 pedigrees / BMI / D8S1121
D2S1788
D6S1008
D17S786
D17S1293 / 3.21
1.16
1.53
1.34
2.33 / SOLAR
Norman RA / AJHG, 1998 / Non-diabetic, Screen / Pima Indians / 127 families, 451 sibpairs / %Fat / 11,111/D11S2366
17,131/D17S785 / 2.1
1.4 / GH
Comuzzie AG / Nature Genetics, 1997 / Pop-based screen / MA, SAFHS / 10 pedigrees (458individuals) / Leptin
Fat Mass / 2,74/D2S1788
2,78/d2s1348 / 4.95
2.75 / SOLAR
MA: Mexican American; pop-based:population-based;ASP:Affected Sib Pair; NIDDM:Non-insulin dependent diabetes;
FCH:Familial Combined Hyperlipidemia; HTN:hypertension;
TOPS:Take Off Pounds Sensibly, Ins.;FUSION: The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics
Study;SAFHS: San Antonio Family Heart Study; SAFADS: San Antonio Family Diabetes Study; HyperGEN: Hypertension Genetic Epidemiology Network;
GENOA: Genetic Network of Atherosclerosis.
GH:GENEHUNTER;GHP:GENEHUNTER-PLUS.
References:
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Comuzzie AG, Hixson JE, Almasy L, Mitchell BD, Mahaney MC, Dyer TD, Stern MP, MacCluer JW, Blangero J: A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nature Genet 15: 273-276, 1997.
DeWan AT, Arnett DK, Atwood LD, Province MA, Lewis CE, Hunt SC, Eckfeldt J: A genome scan for renal function among hypertensives: the HyperGEN study. Am J Hum Genet 68: 136-144, 2001.
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